Since their introduction into clinical practice in the early 1960s, long-acting depot antipsychotics have been widely used as maintenance therapy for patients with schizophrenia. The improved pharmacokinetics of injectable long-acting antipsychotic therapies have provided more reliable drug delivery and reduced differences in peak and trough plasma levels of the drug. Studies that have compared short-acting oral antipsychotics with long-acting injectable antipsychotics, although imperfect, support injectable antipsychotics as having real benefit over oral antipsychotics on patient outcome owing largely to improved adherence. If patients forget or refuse to take their prescribed oral medications, weeks or months may go by before they experience an exacerbation; the effects of nonadherence become apparent too late to preempt the problem. On the other hand, if a patient fails to show up for an injection, the problem of nonadherence can be immediately addressed. When injectable medication is combined with an active psychosocial treatment program that will respond assertively to nonadherence, relapse rates may be reduced. By preventing or delaying relapse, consistent treatment can improve the patient's quality of life and lead to an overall reduction in the cost of care.