Substance use disorders (SUDs) are highly prevalent and are associated with poor outcomes among individuals with schizophrenia. Integrating treatments for both disorders improves outcomes. Numerous individual pharmacologic and psychosocial treatments have shown effectiveness at reducing substance use in individuals with a primary diagnosis of schizophrenia and co-occurring substance use disorders. Of these treatments, medications such as certain atypical antipsychotics and naltrexone, and psychosocial treatments such as contingency management, seem to be particularly promising. The development and evaluation of psychopharmacologic and psychosocial treatments for SUDs in schizophrenia would benefit from a better understanding of the neurobiological mechanisms underlying the effectiveness of such treatments. Several theories have been put forth to explain the heightened risk for SUDs in schizophrenia. Of these, brain reward circuitry dysfunction, hypothesized to be etiologically important in SUDs, may be an especially salient target for treatments aimed at the reduction of substance use in patients with schizophrenia. We review current pharmacologic and psychosocial treatments for SUDs in schizophrenia, and theoretical mechanisms underlying the increased risk for SUDs in this population. We propose that effective treatments may in part work through the modulation of brain reward circuitry dysfunction.