In summary, the cause of NMSC is multifactorial and complex. The interaction among environmental and lifestyle factors along with host factors determines the development and progression of NMSC. Despite the relatively benign nature of NMSC, rising incidence rates in an aging population will result in increased medical costs, morbidity, and mortality. Frequent exposure to UVR, fair skin, and reduced immunity, possibly related to aging, are the major risk factors. Because UVR exposure is responsible for most of the NMSC cases, the key to reducing the number of skin cancers is through prevention, mainly by reducing exposure to sunlight, and further exploration of possible chemopreventive agents. To understand better the complex causes of NMSC and to evaluate prevention strategies, further population-based research is necessary.