The widespread use of atypical antipsychotics (APs) in clinical practice has advanced the pharmacotherapy of schizophrenia regarding treatment resistant cases as well as the negative symptoms of the disorder. Atypical antipsychotics manifest a favourable side effect profile compared to the conventional APs. Atypical APs are also being used as adjunct therapy or monotherapy in patients with manic episodes of bipolar and schizoaffective disorder as well as in patients with psychotic (delusional) depression. On the other hand, atypical APs are also used in combination with (selective) serotonin reuptake inhibitors [(S) SRIs] in the treatment of resistant depression. Shortly after the introduction of atypical APs several cases of manic/hypomanic symptoms during treatment with these compounds have been described in the literature. The reported cases and the possible pathogenetic mechanisms involved in their occurrence are reviewed and discussed.