Cantharidin, a natural toxin produced by the blister beetle, is a topical agent that induces acantholysis of the epidermis, breaking down desmosome plaques through the release of serine proteases. Cantharidin is available in three liquid forms: Ycanth (0.7%), Canthacur (0.7%), and Canthacur PS (1% cantharidin, 30% salicylic acid, 2% podophyllotoxin). Ycanth is used to treat molluscum contagiosum (MC). Canthacur is routinely used to treat a variety of dermatologic conditions including MC, plantar warts, and common warts, whereas Canthacur PS is a more potent formulation indicated for treatment of plantar warts only. The objective of this review is to highlight the efficacy, safety, and diverse use of topical cantharidin in the treatment of various skin conditions. Conditions in which treatment with topical cantharidin yielded a good-to-excellent response include MC, plantar warts, and common warts. Topical cantharidin treatment of anogenital warts yielded mixed results. None of the indications reviewed herein yielded a poor response to topical cantharidin. Overall, topical cantharidin resulted in a good-to-excellent clinical response in several conditions with mild and transient adverse events. The results of this review suggest the safe and efficacious use of topical cantharidin in the field of dermatology and highlight the potential for future use.