Over 40 different antipsychotic medications have been introduced around the world, 21 of which are available in the United States. The conventional antipsychotic drugs introduced in late 50s have two major groups of disadvantages, efficacy and safety. All of the atypical antipsychotic agents have higher 5-HT(2) blocking than D(2) blocking. Atypical antipsychotic agents differ in their receptor action and side effect profile. Among them, clozapine has superior efficacy, and both clozapine and olanzapine have a higher propensity to cause weight gain and possibly diabetes. Quetiapine is difficult to use in acute psychotic states as a result of titration. Ziprasidone and aripiprazole are less sedating, and diabetes as well as weight gain have not been reported with their use. In an acute setting, antipsychotic monotherapy in therapeutic doses is the most useful. AAP drugs are preferred because of the lack of acute EPS symptoms. Intramuscular preparations of haloperidol and ziprasidone are sometimes required to treat acute patients. The goal in acute treatment is to prevent harm to self or others by decreasing excitatory symptoms. Continuing the antipsychotic medication treatment after the acute symptoms are controlled reduces the likelihood of a relapse. The neuroleptic medication should be continued indefinitely. The minimum amount antipsychotic drugs necessary to prevent a relapse should be used, based on clinical decision.