Schizophrenia remains a severe disorder that is associated with a poor outcome in a large subgroup of patients. Major efforts should be made to improve treatment for all patients who have this debilitating disease. Second-generation antipsychotics were a major step forward in this respect; however, important unmet needs remain, such as a better solution for frequent noncompliance problems. Depot formulations are known to have advantages in this respect. However, for a long time, only depot formulations of conventional antipsychotics were available, with their high risk of extrapyramidal adverse effects. Therefore, there has been only very restricted use of depot antipsychotics, which mainly focused on patients with chronic disease who were difficult to treat and had a high risk of noncompliance. The situation may change with the advent of a depot formulation of an atypical antipsychotic. The first depot formulation of an atypical antipsychotic to be introduced to the market is long-acting injectable risperidone. On the basis of the pharmacokinetic properties of the depot formulation, a 2-week interval between administrations is recommended. The antipsychotic efficacy of long-acting risperidone was demonstrated in two 12-week, double-blind, randomised, phase III studies, one versus placebo and the other versus oral risperidone. These two studies, together with one open-label, long-term study over 12 months, belong to the core group of trials that were relevant for the licensing of long-acting risperidone. A relapse-prevention, control group study comparing the long-acting formulation versus oral risperidone was not performed because of the known principal methodological problems of such a comparison. Instead, as much clinical data as possible was collected from observational studies that investigated questions relevant for clinical practice, such as efficacy, safety and tolerability in different subgroups, and transition from pre-treatment with different kinds of antipsychotics to long-acting risperidone. On the basis of these data, it can be stated that the efficacy of the long-term formulation of risperidone is proven, and that the safety and tolerability are more or less comparable to those of oral risperidone. The local tolerability at the injection site is good. Because it is well known that noncompliance is a frequent feature of the treatment of schizophrenia, and considering the advantages of atypical antipsychotics, consideration of whether long-acting atypical antipsychotics should have a broader indication than is the case with the depot formulations of the classical antipsychotics is warranted.