Given the high incidence of non-melanoma skin cancer (NMSC), a preventative intervention would be desirable. Except for regular sunscreen use, the quest for chemoprevention of NMSC in the general population has been unsuccessful. Weinstock et al. assessed the effects of 0.1% topical tretinoin on NMSC. Like earlier efforts at chemoprevention, this study failed to show therapeutic benefit. Future successful preventative strategies will likely rely on short-term, intermittent therapy or treatments used for other common indications.