The therapeutic potential of imiquimod, a toll-like receptor (TLR)-7 agonist, was recognized in the clinical setting more than a decade ago. Beginning with an approved indication for the treatment of external genital warts in 1997, imiquimod 5% topical cream (Aldara) has received further approval for treating actinic keratosis and superficial basal cell carcinoma. Currently, imiquimod 5% topical cream is the most widely studied and characterized TLR agonist available in the clinical milieu. With new formulations and adjunctive regimens being studied, this paper briefly reviews the mechanisms of action, approved indications, exploratory indications and the role of combination therapy, add-on molecules, and new formulations to overcome treatment limitations.