Photomedicine is an interdisciplinary field where chemistry and light meet to fight disease. Photodynamic therapy (PDT) is a special branch of photomedicine that employs a sensitizer molecule, light, and oxygen to destroy target cells with spatiotemporal selectivity. Despite its enormous potential for treating certain diseases, including cancer and infection, PDT has yet to become mainstream. Over the past 10 years, my group has addressed key issues that have hampered bench-to-bedside progress in the field of PDT. Using a multidisciplinary approach, we have introduced both synthetic compounds and natural products (both have successfully completed Phase 1 clinical trials) as alternatives to existing porphyrin-based PDT agents for specific indications. This seminar will share some of our past experiences in developing metallodrug photosensitizers for treating bladder cancer (and photoactive plant extracts for improving oral health if time permits), and will highlight new directions toward the design of immunomodulating theranostic photosensitizers for melanoma PDT.