Acne is a common disorder that may have a considerable psychologic impact including anxiety and depression. Depression and suicide occur frequently in adolescents and young adults. Although case reports suggest an association between isotretinoin and depression and suicide, more rigorous observational studies and epidemiologic studies, using different designs, have not shown any effect of isotretinoin use in increasing the occurrence of depression and suicide. It is prudent for the practitioner to continue to use isotretinoin to treat severe acne, while at the same time informing patients and their relatives that depressive symptoms should be actively assessed at each visit and, if necessary, referral to a psychiatrist and a discontinuation of isotretinoin should be considered.