As an immune-response modifier, imiquimod can bind to Toll-like receptors on immune cells and enhance innate and adaptive immune responses, exerting potential antitumor and antiviral effects, which led to its approval by the US Food and Drug Administration for the treatment of actinic keratosis, superficial basal cell carcinomas, and anogenital warts, and to its off-label use in treating many other benign and malignant dermatoses. Although topical administration of imiquimod has been considered well tolerated, an increasing number of cutaneous and noncutaneous side effects are being reported as its clinical applications expand. This review primarily focuses on rare cutaneous side effects. To the best of our knowledge, this is the first article to summarize the mechanism, diagnosis, and management of rare cutaneous side effects of imiquimod, which may help to heighten awareness among physicians, especially dermatologists, about potential imiquimod-induced cutaneous side effects.