Atypical antipsychotics (aAPs), have become a first-line treatment option, both in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy in acute mania, some also in bipolar depression and in maintenance treatment. This provides reliable data on their safety and tolerability in this particular group of patients. This review focuses on the safety and tolerability of aAPs in the treatment of bipolar disorders. Both tolerability, for example, extrapyramidal symptoms, and safety issues, for example, occurrence of weight gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine, risperidone, ziprasidone and aripiprazole.