Atypical antipsychotics have unequivocally advanced the pharmacotherapy of bipolar disorder. These broad-spectrum medications offer efficacy against core symptoms of mania, and evidence supports the use of several agents as treatment options in depressed and maintenance phases of the disorder. Atypical antipsychotics also have a reduced propensity for provoking acute or tardive neurologic adverse events compared with their therapeutic predecessors, the conventional antipsychotics. These agents are not, however, a panacea and are associated with several problematic tolerability and safety concerns. Although classified together, atypical antipsychotics are heterogeneous in their tolerability and safety profiles, an issue that is relevant to individualizing treatment selection. This article reviews relevant adverse events attributable to the use of atypical antipsychotic agents, with particular consideration of the bipolar disorder population.