This review summarizes the evidence on the protection against skin cancer afforded by sunscreen. Solid evidence can come only from randomized controlled trials, despite a multitude of case-control and cohort studies that have addressed the issue, because observational evidence is intractably confounded since those at highest risk of skin cancer are naturally the highest users of sunscreen. Findings of the single human trial conducted in subtropical Australia during 1992-1996 with follow-up to 2014 showed that the application of a broad-spectrum, sun protection factor 16 sunscreen to exposed skin of the head and neck and upper limbs at least 3-4 days per week in adulthood can reduce the risk of developing cutaneous squamous cell carcinoma and melanoma but does not appear to reduce the risk of basal cell carcinoma (BCC) overall, although it may reduce the occurrence of multiple BCCs over time.