The measurement of health-related quality of life (HRQOL) is increasingly important in patients with skin diseases. Despite the availability of a variety of instruments and new psychometric techniques, there is no consensus as to which HRQOL instruments are to be preferred in dermatology. The objective of this review is to evaluate the generic HRQOL measures (i.e., health profiles) that have been used in dermatology (Short-Form-36 (SF-36) and -12, NHP, SIP, World Health Organization Quality of Life (WHOQOL)-100 and -BREF) and all dermatology-specific HRQOL measures (Dermatology Life Questionnaire Index, Skindex-29, -16, and -17, Dermatology Quality of Life Scales, and Dermatology-Specific Quality of Life). Criteria for evaluation were adapted from existing guidelines and included conceptual and measurement model, reliability, validity, responsiveness, item functioning, meaning of scores, administrative burden, respondent burden, the availability of alternative forms, and of cultural and language adaptations. Furthermore, an overview of skin diseases in which the included HRQOL tools have been used is presented. Although the selection of the appropriate HRQOL instrument remains a trade-off between various psychometric properties and research objectives, for now, we recommend the combination of SF-36 and Skindex-29 as the instruments of choice in dermatology. Promising new instruments for future research are the WHOQOL and the Skindex-17.