In contrast to research studies that limit the use of concomitant psychotropic medications in the treatment of schizophrenia, polypharmacy is common in real-world, clinical practice. The use of psychotropic medications as an adjunct to antipsychotic agents is often necessitated by the poor response to monotherapy with one antipsychotic agent. This paper discusses the prevalence of polypharmacy in clinical settings, reviews the evidence for the adjunctive use of antipsychotics, anticonvulsants, lithium, antidepressants, benzodiazepines and other psychotropics in the treatment of schizophrenia, and offers suggestions toward use of polypharmacy in difficult and practical clinical settings.