Photodynamic therapy (PDT) has become the first-line treatment of actinic keratosis, superficial basal cell carcinoma, and squamous cell carcinoma in situ (Bowen’s disease) in dermatology. The off-label use of PDT has also escalated in recent years owing to its applications in the treatment of various non-neoplastic skin diseases such as acne vulgaris, vascular lesions, rejuvenation, and chronic wounds. Daylight PDT that uses natural sunlight to activate a photosensitizer with advantages such as low cost and reduced pain is widely used in Europe. This chapter reviews the applications and immunogenetic aspects of PDT. However, the studies of immunity and genetic changes in human tissue after PDT are limited.