For decades, psychiatrists worried about the adverse motor effects of antipsychotics and tried to understand what caused them and why some patients developed them and others did not. In the late 1990s, the game changed. The new atypical antipsychotics caused fewer adverse motor effects but caused more weight gain. At present, a large number of patients with schizophrenia experience a clinically important (>7%) weight increase after starting therapy with an antipsychotic. This weight gain contributes to type 2 diabetes mellitus, dyslipidemia, and hypertension, which increase the risk for cardiovascular events. What causes this weight gain? Why do some patients gain weight and others not?