Bipolar disorder places a significant burden on the affected individuals, their family, healthcare systems and the overall economy. More treatment options are needed, especially those with better efficacy and tolerability. Asenapine is a second-generation antipsychotic approved in Europe (brand name Sycrest®) for the treatment of moderate-to-severe manic episodes associated with bipolar I disorder in adults, and in the US (brand name Saphris®) for the treatment of manic or mixed episodes of bipolar I disorder in adults and children aged 10-17 years. It is the antagonistic activity at the D2 receptor that is likely responsible for the antimanic properties of asenapine. Clinical trials have demonstrated that asenapine mono- and add-on therapy is effective in the short- and long-term treatment of mania associated with bipolar I disorder in adult and paediatric patients. In addition, post hoc and pooled data analyses have shown that asenapine is effective in reducing clinically significant depressive symptoms in patients with bipolar I disorder. The most common adverse events associated with asenapine are somnolence, dizziness, extrapyramidal symptoms, increased bodyweight and oral hypoesthesia. However, the incidence of these events, particularly weight gain, is generally lower than with olanzapine. In one study, asenapine has been shown to improve health-related quality of life. Economic analyses indicate that the use of asenapine can, over time, lead to a reduction in the costs of treatment.