Basal cell carcinoma (BCC), the most common and most visible of all human tumors, frequently arises on sun-exposed skin and can produce extensive local damage if left untreated. Targeted therapeutics are now available that interfere with uncontrolled Hedgehog (Hh) signaling, the molecular hallmark of BCC, ushering in a new era in cutaneous oncology. This review describes some of the pivotal work that contributed to our current understanding of BCC and Hh signaling, and ultimately led to the development of drugs targeting the Hh pathway in BCC patients.