Humans have been exposed to solar UV radiation since their appearance on Earth and evolution has enabled most individuals to adapt to this exposure, to some degree. UV radiation produces several deleterious effects in human skin and light-skinned individuals are at greatest risk for both acute and long-term negative effects such as DNA damage, sunburn, immune suppression and skin cancer. The benefits of photoadaptation, which leads to a decreased response after acclimatization, are that humans who have skin that is capable of photoadaptation can work and play in the sun with reduced fear of painful sunburn. However, the effects of photoadaptation on DNA damage and development of skin cancer are quite complex and less well-understood. In this article, we have reviewed the current state of knowledge of UVR photoadaptation in human skin. However, more studies are needed to explore the use of UVR photoadaptation to protect against critical endpoints, such as skin cancer.