The introduction of second-generation antipsychotics represents an important advance in the treatment of schizophrenia. Although these drugs are generally very effective, not all patients respond in the same way. Partial response with persistent positive and negative symptoms and residual symptoms may force physicians to change antipsychotic medication. As more and more second-generation antipsychotics are introduced, the need for practical guidelines on switching these medications becomes increasingly important. In this article we provide a short summary of the second-generation antipsychotics, focusing on efficacy, adverse effect profile and safety. Indications for switching antipsychotic medication are outlined, as well as recommendations when switching is disadvantageous. Three basic switching strategies (abrupt, gradual and overlapping switching) and their potential risks and benefits are described. We review the available evidence concerning techniques, problems and consequences when switching from one second-generation antipsychotic agent to another and discuss potential difficulties.