Today, Bill and Melinda Gates released their latest annual letter, which takes stock of some of the progress they’ve made so far with their philanthropy—but leaves key questions unanswered about where Gates giving might go from here.

I’ll get to those questions in a moment. Let’s first look at the new update, which is titled “Dear Warren,” and takes the form of a letter to Warren Buffett. In December, Buffett—who famously pledged the bulk of his fortune to the Gates Foundation in 2006—asked Bill and Melinda to reflect on how they’re measuring their progress and how they “would like the final scorecard to read.”

Their response is a sweeping and uplifting look at gains the world has made in improving global health in the past 25 years, especially when it comes to reducing child mortality. The letter notes that childhood deaths have been cut in half since 1990, with 122 million lives saved as a result.

The Gateses write further that vaccines have been the biggest reason for this drop. Bill and Melinda say, “Coverage for the basic package of childhood vaccines is now the highest it’s ever been, at 86 percent. And the gap between the richest and the poorest countries is the lowest it’s ever been.”

That’s a remarkable statistic, and expanding access to vaccinations, of course, has been a central focus of the Gates Foundation’s work since its inception. To the extent that their philanthropy has played a key role, here—along with that of other donors—it’s a stunning testament to the power of private giving to shape the arc of human history.

(I don’t know of any authoritative study measuring the exact role of the Gates Foundation in expanding vaccination coverage and how many lives have been saved as a result. One analysis estimated that between 2007 and 2012, investments by the foundation saved around 6 million lives.)

Looking ahead, the Gateses see even bigger gains to come. They write, “In our lifetimes, malaria will end. No one will die from AIDS. Few people will get TB. Children everywhere will be well nourished. And the death of a child in the developing world will be just as rare as the death of a child in the rich world.”

Those seem like remarkably optimistic predictions, but the Gateses don’t say much about their game plan going forward to conquer top dread diseases and greatly reduce the extreme poverty that underlies the suffering of children worldwide.

More broadly, this annual letter—like previous ones—doesn’t offer much insight into the couple’s thinking about how they will handle the monumental task of deploying vast piles of wealth going forward.

Consider three figures: First, the Gates Foundation, which will spend down and close its doors two decades after Bill and Melinda die, has an endowment of some $40 billion. Second, according to Forbes, Bill Gates’s net worth is now $85 billion, a fortune that he and Melinda have said they will give away. Third, Warren Buffett is currently worth $74 billion, with maybe $60 billion of that destined for the Gates Foundation.

All these numbers will likely change, perhaps declining sharply if there is a stock market correction. On the other hand, both Gates and Buffett could potentially grow much richer in the next decade or so, since both have added tens of billions to their fortunes since 2006.

But to keep things simple, let’s work with today’s numbers: Over the next half-century or so, Bill and Melinda, along with whoever handles their giving once they’re gone and their foundation is spending down, may dedicate as much as $185 billion in total to their philanthropic mission. By comparison, since its inception, the Gates Foundation has spent around $40 billion. So we’re looking at four times as much money harnessed to Gates giving over future decades.

Here are four questions about what lies ahead.

Will the Gates Foundation Increase Its Grantmaking, and If So, When?

Over the past few years, Gates Foundation giving has held pretty steady. In 2015, it made $4.2 billion in grants; the year before, it was $3.9 billion. Yet, with so much money waiting in the wings, the Gateses could easily raise their level of annual giving—and at some point, will need to do so in order to achieve their long-term spend-down ambitions.

I’ve wondered before why the Gateses aren’t giving away more money, faster—even as they’ve exhorted other wealthy people to give and even as they’ve trumpeted the immense value of making preventive investments today, starting with vaccinating children. I suspect they have very good reasons for holding back, such as wanting to be sure greater giving has the desired impact or because their grantmaking pipeline can only handle so much money. Regardless, it’d be nice to know what the schedule is, here—assuming they themselves know. (Maybe they don’t.)

Will Bill and Melinda Embrace New Causes?

One way to give away lots of money faster is to embrace a broader agenda. You can see that most vividly in Mike Bloomberg’s giving, which now ranges far more widely than it did a few years ago, with this billionaire tackling such new areas as protecting the world’s fisheries. Will Bill and Melinda also move into new areas?

There are some signs of things moving in this direction. Gender equity has emerged as a growing focus on the Gates Foundation’s international work in recent years, with Melinda taking the lead. Domestically, the foundation has started to expand into early childhood learning, as we’ve reported. Even more intriguing, the Gates Foundation launched a wide-ranging effort last year to explore U.S. poverty issues, tapping a who’s who of leading thinkers. It’s hard to say where that initiative might lead, but it would obviously be huge news to the nonprofit world if the Gates Foundation’s U.S. work departed from its narrow education focus and tackled inequities writ large. Such an expanded agenda could also absorb many billions of dollars.

One other thing: Last year, Bill Gates launched a big investing effort on clean energy, which shows that he’s thinking about the challenge of climate change. Might the foundation one day take this on through its grantmaking? It would make sense, given that so many of humanity’s recent gains will be at risk in the coming century and beyond as the climate changes.

Will the Gateses Upend How They Approach Existing Areas of Work?

Bill and Melinda’s latest annual letter focuses strictly on their global work, and mainly on the health parts of that work. You can see why, too: This has been where they’ve had their greatest success as philanthropists. Meanwhile, other areas haven’t gone nearly as well, starting with their massive push to improve K-12 education in the United States—an effort that, by Bill’s own account, has not produced dramatic change. Others, of course, have offered far harsher accounts of the foundation’s performance.

Will we see a very different Gates approach to K-12 going forward? We’ve speculated quite a bit on this lately at IP, looking at the recent appointment of Bob Hughes to lead the K-12 work. Hughes is known as a stronger collaborator, so perhaps the era of the Gates Foundation charging forward with grand and risky experiments (with hugely disruptive effects) is coming to an end. Regardless, it would be nice to hear Bill and Melinda offer both a frank retrospective of their K-12 work to date and thoughts on their plans going forward.

Will Impact Investing Move Front and Center?

As I mentioned, Bill Gates has an $85 billion private fortune that has not yet been harnessed to philanthropy. And just maybe it never will be. Maybe that money will be mainly directed to impact investing, like the clean energy effort that Gates has put together. As we’ve reported, the Gates Foundation already leads the foundation world in terms of the sheer dollars that it has put into private investments and, presumably, it’s learned a lot along the way. Meanwhile, more and more donors are realizing that traditional grantmaking is a very limited tool for tackling some of humanity’s biggest challenges. If Bill and Melinda really drink the Kool Aid here, it could have big implications for what comes.

Maybe the endgame of Gates philanthropy involves less and less straight giving. Maybe a few decades from now, the bulk of that huge remaining Gates fortune will be in a social investment fund with the potential to exist for a very long time to come.

I guess we’ll see.