Rates of skin cancer continue to increase despite the improved use of traditional sunscreens to minimize damage from ultraviolet radiation. The public perception of tanned skin as being healthy and desirable, combined with the rising demand for treatments to repair irregular skin pigmentation and the desire to increase or decrease constitutive skin pigmentation, arouses great interest pharmaceutically as well as cosmeceutically. This review discusses the intrinsic biochemistry of pigmentation, details mechanisms that lead to increased or decreased skin pigmentation, and summarizes established and potential hyper- and hypo-pigmenting agents and their modes of action.