Isotretinoin is a very effective medication for the treatment of severe recalcitrant acne. However, its use is associated with many side effects, some of which can be very serious. The most important issue is its teratogenicity, which has resulted in new pregnancy prevention policies and programmes implemented by the manufacturer. Recently, the association of isotretinoin with depression has been recognised and new guidelines have been adopted for this possible side effect. The most common adverse events, observed during treatment, are mucocutaneous and ophthalmological. In addition, laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary and other systems have been described.