We know that Apple has been making a killing from the iPhone, with the device reigning as the single-most popular smartphone in a number of markets — despite Android-based handsets collectively having a bigger lead. Now, with the fifth anniversary of the iPhone fast approaching — it’s June 29 — Strategy Analytics has calculated just how big that killing is: Apple has shipped 250 million iPhones worldwide, and the iPhone has generated $150 billion in cumulative revenues, it estimates.

The figures cover the entire family of iPhone devices — from the first model released in 2007 through to the most recent iPhone 4S. Of them, Strategy Analytics tells me that the device that has topped the list has been the iPhone 4 — both in terms of price and volume. However, there is a dark shadow around today’s news, too. Strategy Analytics believes that if the first five years were awesome, the next five will be a lot more challenging, for several reasons:

For one, smartphone market growth is slowing; Android competitors like Samsung are continuing to ramp up their efforts; and operators are getting more impatient with the subsidies the offer on iPhones — which are priced at a premium compared to Android handsets but often get discounted heavily by carriers in exchange for users signing up to big data plans. In some cases, those phones are free.

“There are emerging signs that the iPhone’s next five years could get tougher,” analyst Neil Mawston said in an emailed statement. “Some mobile operators are becoming concerned about the high level of subsidies they spend on the iPhone, while Samsung is expanding its popular Galaxy portfolio and providing Apple with more credible competition.”

But credible competition or not, all handset makers will be selling in an increasingly tight market, with smartphone penetration in parts of the world like the U.S. and Europe approaching a majority of phone users. Strategy Analytics estimates that in Q2 2012, handset shipments have grown by a “sluggish” 4 percent, partly due to economic slowdowns in Europe, Asia and North America.

On the other hand, if Apple comes through with a new iPhone model, and those making 4G devices continue to produce compelling products, these figures could get better in the second half of this year.

Apple’s next quarterly results, covering Q3, will be out in July.