Background: In the past 30 years, topical photodynamic therapy (PDT) has been investigated for the treatment of a broad spectrum of cosmetic, inflammatory, and infectious skin conditions with variable, and often contrasting, results. However, the non-expert clinician may be in difficulty evaluating these results because different sensitizers, concentrations, formulations, light sources, and irradiation protocols have been used. In addition, many of these studies have poor quality design being case reports and uncontrolled studies of few cases. Summary: With the aim to clarify the potential usefulness of PDT for the treatment of infectious and inflammatory skin diseases as well as selected cosmetic indications, we searched for randomized controlled clinical trials, non-randomized comparative studies, retrospective studies, and case series studies with a number of at least 10 patients, published since 1990. Later, we reappraised the results in order to give a simple critical overview. Key Messages: Evidence from the literature seems to strongly support the use of ALA- and MAL-PDT for the treatment of common skin diseases such as acne, warts, condylomata, and Leishmania skin infection and for photorejuvenation, i.e., the correction of selected cosmetic changes of aging and photoaging. For other disorders, the level of evidence and strength of recommendation are lower, and controlled randomized studies with prolonged follow-ups are necessary in order to assess the clinical usefulness and other potential advantages over current treatment options.