Psychiatric syndromes, including depression, obsessive-compulsive disorder, panic, and substance use disorders, co-occur with schizophrenia at significant rates. These syndromes interact with schizophrenia symptoms in clinically meaningful ways, and can be associated with adverse outcomes such as suicide, long-term disability, medication nonadherence, and frequent hospitalization. Data to inform treatment of co-occurring syndromes are largely anecdotal, and further studies are required to understand better the risks and benefits of treatment options. Weight gain and disturbances of glucose and lipid metabolism are emerging as significant medical comorbidities in patients treated with new-generation antipsychotic agents, and preventive interventions are urgently needed.