There is increasing evidence that longwave ultraviolet (UV) radiation (UVA; 320-400 nm) plays an important role in the pathogenesis of photodermatoses such as polymorphous light eruption as well as photoaging. In order to fully understand these detrimental effects it is critical to analyze the photobiological and molecular mechanisms by which UVA radiation affects the function of human skin cells. In this review, our current knowledge about the signal transduction pathway involved in UVA radiation-induced expression of proinflammatory genes relevant to the pathogenesis of polymorphous light eruption will be summarized. In addition, recent studies on the role of mitochondrial DNA mutations in UVA radiation-induced photoaging of human skin will be discussed. For both biological endpoints the UVA radiation-induced generation of singlet oxygen within human skin appears to be of critical importance. These studies are of enormous clinical relevance because they indicate that prevention of the generation of singlet oxygen or inhibition of singlet oxygen-induced signaling pathways may prove to be critical for effective protection of human skin against UVA radiation-induced damage.