The human body is constantly exposed to exogenous and endogenous insults that threaten its genomic integrity and that lead to changes at the molecular, biochemical, and cellular levels. As a major interface between the environment and the internal milieu, our skin is especially subject to such events. Common insults include but are not limited to infectious agents, environmental pollutions and toxins, carcinogens, and ultraviolet (UV) irradiation. It is estimated that there are thousands of DNA alterations in each cell daily. Therefore, if not efficiently repaired, our genome would rapidly be destroyed. This review focuses predominantly on UV-induced DNA damage in human skin, protective molecular responses to UV damage, and the consequences of these opposing forces for aging and photocarcinogenesis.