The expression of heat shock proteins (Hsp) expression is induced in all cells by exposure to heat and other environmental stress and Hsp can protect cells from damage through further exposure. Hsp are highly conserved and it is likely that they are essential for survival in a potentially harmful environment. Most Hsp are molecular chaperones sensing unfolded proteins and mediating their re-folding, transport, and interaction. In human epidermis Hsp are associated with differentiation, photoprotection, and skin disease. Recent research has mainly focused on the 27kD and 72kD Hsp that are constitutively expressed in keratinocytes. Cell death induced by ultraviolet radiation (UV) can be inhibited by previous heat shock and UV itself can induce Hsp experimentally. Regulation of Hsp can be pharmacologically modified and topical and systemic inducers and inhibitors of Hsp expression are under development. Whether phototherapy exerts its clinical efficacy by modulation of Hsp has not been sufficiently studied. The UV-wavelength ranges, -intensities and -doses that are required to interfere with the heat shock response in the skin still remain to be elucidated.