Photodynamic therapy (PDT) is an innovative combination therapy that integrates pharmaceutical and technological approaches for disease diagnosis and treatment. Photodynamic reactions rely on three fundamental components—photosensitizers, light, and oxygen molecules—to induce photodynamic reactions, which can be classified into type I and II reactions, both of which lead to cytotoxic effects and cellular damage. The mechanisms of PDT include direct cytotoxicity to target cells, vascular injury, and immunological responses. Direct cytotoxicity is the result of oxidative reactions that induce cell death through pathways such as apoptosis, necrosis, and autophagy. Vascular injury occurs through damage to endothelial cells, leading to vascular occlusion and hypoxia in the targeted tissues. Immunological mechanisms involve activating the immune system, promoting antitumor immunity, and the formation of tertiary lymphoid structures. Various photosensitizers, such as 5-aminolevulinic acid (ALA), hemoporfin, and their derivatives, are used in PDT. Each has distinct characteristics and applications, and the choice of photosensitizer is crucial for the effectiveness of PDT. PDT has shown promise in treating a wide range of diseases, including cancer and nonmalignant conditions. In basic research on PDT, numerous cell and animal models have been widely used to investigate the efficacy, safety, parameters, and mechanisms of this treatment for various skin diseases. These research models are essential tools for obtaining a deeper understanding of PDT, and they are also briefly introduced in this chapter.