With increasing demand for the accurate and safe treatment of cancer, non-invasive photodynamic therapy (PDT) has received widespread attention. However, most conventional photosensitizers are typically excited by short-wavelength visible light (400–700 nm), thus substantially hindering the penetration of light and the therapeutic effectiveness of the PDT procedure. Fortunately, near-infrared (NIR) light (>700 nm), in particular, light in the second near-infrared region (NIR-II, 1000–1700 nm) has a higher upper radiation limit, greater tissue tolerance, and deeper tissue penetration compared with traditional short-wavelength light excitation, and shows considerable potential in the clinical treatment of cancer. Therefore, it is of paramount importance and clinical value to develop photosensitizers that are excited by NIR-II light. In this review, for the first time we focus completely on recent progress made with various NIR-II photosensitizers for cancer treatment via PDT, and we briefly present the ongoing challenges and prospects of currently developed NIR-II photosensitizers for clinical practice in the near future. We believe that the above topics will inspire broad interest in researchers from interdisciplinary fields that include chemistry, materials science, pharmaceuticals, and clinical medicine, and provide insightful perspectives for exploiting new NIR-II photosensitizers for biomedical applications.