Ultraviolet radiation (UVR) is known to be one of the most important environmental hazards acting on the skin. It was revealed that chronic exposure to UVR accelerates skin aging, induces immunosuppression and may lead to the development of skin cancers. On the other hand, UVR has been shown to be effective in the treatment of numerous skin diseases and thus, various phototherapy modalities have been developed to date. Narrow-band ultraviolet B (NB-UVB) emitting a light with a peak around 311 nm has been demonstrated to be effective in the treatment of various skin disorders; currently it is one of the most commonly used phototherapy devices. Despite NB-UVB has been developed more than 30 years ago, the exact mechanism of its therapeutic action remains poorly understood. To date, most of NB-UVB effects were attributed to its influence on immune cells; however, nearly 90% of NB-UVB irradiation is absorbed by epidermis and keratinocytes seem to be important players in mediating NB-UVB biological activity. Here, we have reviewed the current data about the influence of NB-UVB on epidermal cells, with a special emphasis on cell proliferation and death.