ALA-PDT is widely used to treat various skin diseases, but pain during and after therapy remains a common and significant adverse event, often hindering its clinical use. Effective pain management during PDT is crucial for enhancing patient comfort and broadening ALA-PDT applications. Recent research from the authors’ group investigated the associations between pain perception and various factors, including photosensitizer concentration, treatment duration, light dose, and light source selection. These findings revealed that daylight photodynamic therapy (DL-PDT) and modified 5-aminolevulinic acid photodynamic therapy (M-PDT) are superior in maintaining therapeutic effectiveness while minimizing pain. These explorations not only revealed the potential to achieve patient comfort during PDT but also expanded the use of PDT in clinical practice.