Imiquimod (Aldara, 3M Pharmaceuticals) is a potent stimulator of the innate and adaptive arms of the immune system through induction, synthesis, and release of cytokines and chemokines. An extensive review of clinical trials, case reports, and letters published in peer-reviewed journals was performed regarding imiquimod use in skin disorders. A reference module was developed for physicians to consult as a guide. Studies have validated the benefit of imiquimod in treating external genital and perianal warts, superficial basal cell carcinomas, and actinic keratoses. This new topical therapeutic agent has shown to be of benefit in other various skin disorders through its broad immunomodulatory properties. Since many skin conditions are immunologically influenced, it is reasonable to expect several diseases to respond to imiquimod. Our research consolidates the therapeutic trials and reports on the innovative uses of imiquimod, thereby serving as a useful resource to benefit dermatologists treating patients with refractory or recalcitrant skin diseases.