Phototherapy and photochemotherapy are important treatment regimens for inflammatory as well as malignant diseases in dermatology. Both treatment modalities have been developed already three decades ago and therefore profound knowledge exists on the use, efficacy, and long-term side effects. Since the development of new mmunosuppressive medications, biologics, and changes in medical reimbursement policies, phototherapy is currently less frequently used compared to previous years to treat psoriasis or atopic dermatitis. However, cost-effectiveness analysis demonstrated that phototherapy can significantly induce therapeutic beneficial effects on a large number of inflammatory and malignant skin disorders at a low cost of treatment rate. Since many chronic skin disorders require rotational treatment regimens to decrease the development of (long-term) adverse events, phototherapy will play an important role in dermatology in future years. In the following the molecular as well as cellular mechanisms of phototherapy are described and discussed in light of the fact that photobiology is a very active field in biomedical research.