Bailey et al. report in this issue of the journal (beginning on page 35) one of the first successful trials of basal cell carcinoma (BCC) prevention. Oral α-difluoromethyl-dl-ornithine (DFMO) reduced new BCCs in patients with a prior history of nonmelanoma skin cancer. DFMO is an inhibitor of ornithine decarboxylase, a key enzyme in the polyamine biosynthetic pathway. This perspective on Bailey et al. discusses our knowledge of the contribution of polyamines to BCC pathogenesis, how this knowledge advanced the development of a new method to prevent BCCs, and prospects for future studies of DFMO in BCC prevention. ©2010 AACR.