Photodynamic therapy (PDT) and nonfluorescence diagnosis (PPD) are widely applied in dermatology and other medical fields, with ALA-PDT being the most established method for skin diseases. This book comprehensively reviews PDT’s evolution, emphasizing advances in photosensitizers, light sources, mechanisms, and pain management. Clinical applications of ALA-PDT cover over 3000 Chinese hospitals, treating skin cancers, HPV-related diseases, follicular disorders, hemangiomas, and refractory conditions like extramammary Paget’s disease. PDT faces challenges globally, including limited recognition, resistance in deep-tissue cancers, and pain management. The key future directions include: (1) Enhancing PDT Efficiency: Developing targeted nanoloaded photosensitizers, novel light sources (upconversion materials, nonlaser irradiation), and immune adjuvants to boost antitumor efficacy and overcome resistance. (2) Neoadjuvant PDT in Cancer: Integrating PDT with immunotherapy to remodel the tumor microenvironment and improve outcomes for resistant cancers. (3) Expanding Clinical Indications: Advancing PDT for infectious diseases, granulomatous disorders, and fungal infections, leveraging its nonresistance profile and biofilm disruption potential. (4) Painless PDT Innovations: Implementing two-step illumination and sunlight-based protocols to mitigate discomfort, particularly in systemic treatments. (5) Home PDT Systems: Promoting home-based devices and microneedle patches for accessible, cost-effective care for acne, aging, and chronic skin conditions. This book underscores PDT’s role as a minimally invasive, repeatable modality with immense potential. Addressing technical bottlenecks, optimizing treatment protocols, and raising public awareness will further revolutionize PDT in dermatology and oncology, enhancing patient outcomes globally.