Antipsychotics have for half a century been the mainstay for the pharmacological management of schizophrenia patients. While efficacy has been the primary outcome variable in short term clinical trials many additional variables need to be accounted for when judging the usefulness of these medications over longer periods of time. Classic continuation studies and relapse prevention trials have mostly focused on symptom control, while safety/tolerability and subjective acceptance of these medications have generally been seen as secondary outcome measures. The concept of effectiveness attempts to provide a comprehensive outcome variable which encompasses all the relevant issues that determine longer term treatment success. Lately a number of large scale effectiveness trials, sometimes called large pragmatic clinical trials, have been undertaken, especially in the context of the attempt to evaluate differential drug effects. CATIE and CUTLASS have already been published, CAFE data have been presented in rough outlines and EUFEST results are still pending. While the first two studies have included patients with chronic schizophrenia, first episode patients have been allocated to the latter two trials. Although the available results from these trials are discussed very controversially, they unquestionably present an important addition to the traditional randomized controlled clinical trial design. Information from all types of research will have to be amalgamated in order to allow a rational choice for the long term management of schizophrenia patients. Unfortunately, the results available so far do not allow generalizable statements with regard to differential efficacy/effectiveness of antipsychotic drugs in the long term management of schizophrenia.