The search is on for meaningful psychopharmacological and cognitive/behavioral interventions for neurocognitive deficits in schizophrenia. Findings in this area are emerging rapidly, and in the absence of integrating frameworks, they are destined to emerge chaotically. Clear guidelines for testing neurocognitive interventions and interpreting results are critical at this early stage. In this article, we present three models of increasing complexity that attempt to elucidate the role of neurocognitive deficits in schizophrenia in relation to treatment and outcome. Through discussion of the models, we will consider methodological issues and interpretive challenges facing this line of investigation, including direct versus indirect neurocognitive effects of antipsychotic medications, selection of particular neurocognitive constructs for intervention, the importance of construct validity in interpreting cognitive/behavioral studies, and the expected durability of treatment effects. With a growing confidence that some neurocognitive deficits in schizophrenia can be modified, questions that seemed irrelevant only a few years ago are now fundamental. The field will need to reconsider what constitutes a successful intervention, what the relevant outcomes are, and how to define treatment efficacy.