Recent success using mTOR (mammalian target of rapamycin) inhibitors such as rapamycin for the systemic manifestations of tuberous sclerosis exemplify how targeted therapy can treat genetic disorders. Haemel and colleagues describe the novel use of topical rapamycin in a petrolatum vehicle for facial angiofibromas in a patient with tuberous sclerosis. Since its publication, several authors have similarly reported successfully using various compounds of rapamycin or even the topical application of the commercially available oral solution for facial angiofibromas. Topical application of the oral solution is associated with local irritation that necessitates topical steroids. Compounded rapamycin is at least 10-fold more expensive than a similar amount of the oral solution. Rapamycin therapy is expensive, but the cost must be compared with alternative therapies, including pulsed dye or ablative lasers, that often require general anesthesia in this population. Prospective studies are needed to clarify the pharmocokinetics of topically applied rapamycin and the optimal formulation, dosing, duration, monitoring, and safety of this therapy.