The development of nanotechnology has changed the 100-year-old paradigm of photodynamic therapy (PDT), in which organic/inorganic hybrid nanomaterials have made great contributions. In this review, we first describe the mechanisms of PDT and discuss the limitations of conventional PDT. On this basis, we summarize recent progress in organic/inorganic nanohybrids-based photodynamic agents, highlighting how these nanohybrids can be programmed to overcome challenges in photodynamic cancer therapy.