SignificanceHerbal medicine is an important part of the health care system in many countries as they exhibit chemopreventive and chemotherapeutic effects. The combination of phytochemicals with Photodynamic therapy is a novel approach to enhancing therapeutic efficacy. ApproachWe studied the effect of various plant extracts, phytochemicals, photosensitizers and their combinations to induce cell death in the lung, breast, colon, cervical and skin cancer cells. The efficacy of the drug moieties was evaluated using viability, proliferation, and cytotoxicity studies. Detailed cell death mechanism was studied using protein expression profiling using immunofluorescence, flow cytometry, ELISA and western blotting. ResultsThe results revealed that PDT and combination therapy groups showed significant cell death in breast and lung cancer cells. Conjugation of photosensitizers with nanoparticles and phytochemicals enhanced the drug delivery and treatment outcome. ConclusionsCombination of PDT with other existing treatments or replacing the synthetic PSs with natural ones is a promising approach in the fight against cancer with improved specific cancer cell targeting.