Cognitive deficits are a central and debilitating aspect of schizophrenia and other major mental illnesses. Although they are largely refractory to pharmacotherapy, multiple studies have now shown that large and lasting improvements in cognition can result from behavioral interventions. We will review our work over the past 10 years demonstrating that cognitive remediation treatment together with work therapy or supported employment can lead to large, lasting, and clinically relevant improvements in cognition and work functioning. While we will make some references to the work of others in these same areas, this is not a general review of these areas of research. Instead, the goal is to provide the rationale for the progression of our studies, describe the methods, and summarize the results, so that readers may understand, critique, and improve upon what we have done.