Photodynamic therapy (PDT) is a well-studied treatment for cancer and various non-malignant diseases, utilizing photosensitizers (PSs) that are activated by visible light to form reactive oxygen species (ROS). The dual-specificity of PDT relies on the accumulation of PSs in diseased tissue and localized light delivery. Tetrapyrrole structures, such as porphyrins, chlorins, bacteriochlorins, and phthalocyanines, have been widely investigated and several compounds have received clinical approval. Other molecular structures, including synthetic dyes, transition metal complexes, and natural products, have also been explored. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins, and other ligands with specific cellular receptors. Nanotechnology has significantly contributed to PDT, with approaches including nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and upconverting nanoparticles to enhance light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.Photodynamic therapy (PDT) is a well-studied treatment for cancer and various non-malignant diseases, utilizing photosensitizers (PSs) that are activated by visible light to form reactive oxygen species (ROS). The dual-specificity of PDT relies on the accumulation of PSs in diseased tissue and localized light delivery. Tetrapyrrole structures, such as porphyrins, chlorins, bacteriochlorins, and phthalocyanines, have been widely investigated and several compounds have received clinical approval. Other molecular structures, including synthetic dyes, transition metal complexes, and natural products, have also been explored. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins, and other ligands with specific cellular receptors. Nanotechnology has significantly contributed to PDT, with approaches including nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and upconverting nanoparticles to enhance light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.