Photodynamic therapy (PDT) is a light-based intervention with a long and successful clinical track record for both oncology and non-malignancies. In cancer patients, a photosensitizing agent is intravenously, orally or topically applied and allowed time to preferentially accumulate in the tumor region. Light of the appropriate wavelength and intensity to activate the particular photosensitizer employed is then introduced to the tumor bed. The light energy will activate the photosensitizer, which in the presence of oxygen should allow for creation of the toxic photodynamic reaction generating reactive oxygen species. The photodynamic reaction creates a cascading series of events including initiation of apoptotic and necrotic pathways both in tumor and neovasculature, leading to permanent lesion destruction often with upregulation of the immune system. Cutaneous phototoxicity from unintentional sunlight exposure remains the most common morbidity from PDT. This paper will highlight current research and outcomes from the basic science and clinical applications of oncologic PDT and interpret how these findings may lead to enhanced and refined future PDT.