The quest for procedures to fight cancer is a health priority. The impacts of tobacco, obesity, and infections are just part of a broad spectrum of other agents and risk factors that have contributed to the development of various forms of cancer. As never before, there is an urgent need for improved treatments and early detection of the disease. Photodynamic therapy (PDT) is a form of photochemotherapy approved in the clinical treatment of cancer that combines visible light, oxygen, and a light-activated molecule designated by photosensitizer (PS). Being a noninvasive technique with high cure rates and low side effects, PDT is considered a very appealing alternative to conventional cancer treatments. This chapter summarizes the current developments and challenges of PDT application, highlighting the main achievements made in this therapeutic treatment in recent years, especially in improving PS activity and light sources, while providing guidance for future developments. A brief historical update is presented, followed by a description of the PSs currently tested to treat cancers, including esophageal, lung, head, neck, prostate, and skin cancers. How PDT works, how it can be used to treat cancer, and how it can be used in combination with immunotherapy through photodynamic immunotherapy (PDI) are topics to be covered throughout this chapter.