Cancer is one of the leading causes of death worldwide with high rate of recurrence even after modern medical intervention. Various treatment approaches, such as chemotherapy, radiation therapy, and targeted gene therapy, have been developed to combat cancer. However, these treatments often come with significant drawbacks, including high costs and severe side effects, which can hinder their effectiveness and reduce patient quality of life. Photodynamic therapy (PDT) is a novel clinical technique that uses photosensitive chemicals known as photosensitizers (PSs) to become cytotoxic when activated by light of a specific wavelength in the presence of oxygen. When activated, the PSs produce reactive oxygen species (ROS), which cause cellular damage and result in the removal of aberrant or malignant cells. Because of its capacity to selectively target cells while avoiding damage to surrounding healthy tissue, PDT is increasingly being used to treat various cancers, particularly surface tumors or benign malignancies, microbial infections, and other medical conditions. This chapter provides an insight into the fundamental chemical and biological concepts that underpin PDT, with a special emphasis on its applications in cancer treatment. It discusses the mechanisms underlying PDT, in which PSs are activated by light to produce ROS capable of selectively destroying cancer cells. This chapter also discusses the current limitations and developments in PDT, particularly in terms of its effectiveness. It examines the issues of improving PS delivery systems and tumor targeting, as well as strategies for overcoming barriers such as tumor hypoxia and poor light penetration. Advances in nanotechnology, such as the invention of nanoparticle-based carriers, are being investigated as methods to increase PS administration, ensure more effective tumor localization, and address oxygen deprivation in tumor microenvironments. Furthermore, efforts to improve light penetration, notably using near-infrared (NIR) light and two-photon excitation, are highlighted, with the goal of improving PDT’s efficacy in treating deep-seated cancers.