Mounting evidence indicates that schizophrenia is a disorder that stems from maladaptive plasticity within neural circuits and produces broad cognitive deficits leading to loss of autonomy. A large number of studies have identified abnormalities spanning many neurotransmitter systems in schizophrenia, and as a result, a variety of drugs have been developed to attempt to treat these abnormalities and enhance cognition. Unfortunately, positive results have been limited so far. This may be in part because the scope of abnormalities in the schizophrenic brain requires a treatment capable of engaging many different neurotransmitter systems. One approach to achieving this kind of treatment has been to use neuroplasticity-based computerized cognitive training programs to stimulate the formation of more adaptive circuits. Although the number of studies implementing this approach has increased exponentially in recent years, effect sizes for cognitive gains have been modest and adherence to treatment remains an important challenge in many studies, as patients are often required to train for 40 h or more. In the present paper, we argue that cognitive training protocols will benefit from the addition of cognitive enhancers to produce more robust and longer lasting targeted neuroplasticity. Indeed, recent data from animal studies have provided support for combining plasticity-enhancing drugs with tailored behavioral training paradigms to restore normal function within dysfunctioning neural circuits. The advantages and challenges of applying this approach to patients with schizophrenia will be discussed.