Systemic isotretinoin has been used to treat severe acne vulgaris for 20 years. However, isotretinoin also represents a potentially useful choice of drugs in many dermatologic diseases other than acne vulgaris. Diseases such as psoriasis, pityriasis rubra pilaris, condylomata accuminata, skin cancers, rosacea, hidradenitis suppurativa, granuloma annulate, lupus erythematosus and lichen planus have been shown to respond to the immunomodulatory, anti-inflammatory and antitumor activities of the drug. Isotretinoin also helps prevent skin cancers such as basal cell carcinoma or squamous cell carcinoma. A combination of systemic isotretinoin and interferon-alpha-2a may provide a more potent effect than isotretinoin alone in the prevention and treatment of skin cancers.