While most basal cell carcinomas (BCCs) are amenable to resection, surgical intervention is impractical for patients with metastatic or locally invasive BCCs or cancer predisposition syndromes, such as basal cell nevus syndrome. Until now, treatments for these nonsurgical candidates met with limited efficacy. The causal role of aberrant hedgehog signaling in BCCs has led to the recent exploration of hedgehog pathway inhibitors as a targeted therapy, and, as shown by Goldberg et al last year, the smoothened antagonist GDC-0449 [2-chloro-N- (4-chloro-3-[pyridin-2-yl]phenyl)-4-(methylsulfonyl)benzamide] can achieve clinical regression in basal cell nevus syndrome. Since Goldberg and colleagues' article was published, GDC-0449 has demonstrated efficacy against advanced BCCs and metastatic medulloblastoma, and hedgehog pathway inhibitors are currently under clinical investigation for several other lethal cancers. Hedgehog pathway inhibitors offer a new adjuvant medical therapy for advanced and, if trials demonstrate effectiveness, early-stage BCCs.