Antipsychotic treatment with so-called "atypical" neuroleptics, as defined by the lack of extrapyramidal side effects in its strict sense, has made great advances in the last decades with the advent of newly developed antipsychotic agents. The first atypical neuroleptic drug was clozapine, also referred to as "dirty drug" or "rich drug" because of its broad receptor binding profile. Clozapine has been the starting point for several different, newly developed antipsychotics. Among these, the most prominent are olanzapine, risperidone, sertindol, ziprasidone, and amisulpride. All of these newly developed, atypical antipsychotics show a high degree of efficacy in the treatment of positive symptoms of schizophrenia in combination with a lack of or a reduced degree of extrapyramidal side effects (EPS). In addition, several atypical antipsychotics seem to have an additional impact on negative symptoms such as alogia, anhedonia, or avolition. However, apart from the clear advantage of clozapine in the treatment of otherwise treatment-resistant schizophrenia, differential indications for the different antipsychotics remain to be established.