Photodynamic therapy (PDT) is a promising cancer treatment that uses photosensitizing (PS) compounds to selectively destroy tumor cells using laser light. This review discusses the main advantages of PDT, such as its low invasiveness, minimal systemic toxicity, and low risk of complications. Special attention is paid to photosensitizers obtained by chemical synthesis. Three generations of photosensitizers are presented, starting with the first generation based on porphyrins, through the second generation including modified porphyrins, chlorins, 5-aminolevulinic acid (ALA), and its derivative hexyl aminolevulinate (HAL), to the third generation, which uses nanotechnology to increase therapy selectivity. Current research trends include the search for new photosensitizers that can overcome the limitations of existing therapies, such as heavy-atom-free nonporphyrinoid photosensitizers, antibody–drug conjugates (ADCs), or photosensitizers with a near-infrared (NIR) absorption peak. The review highlights the development of PDT, considering advances in nanotechnology and biomedical engineering. The references include both older and newer works. The article includes reviews and research articles, as well as case reports. The keywords are PDT and synthetic photosensitizers. The review discusses the application of PDT in cancer therapy, focusing on advances in the creation of novel photosensitizers. The review is based on research from PubMed and Google Scholar on the use of PDT in cancer treatment, with a focus on the role of synthetic photosensitizers. The collected articles were published between 1984 and 2024. A total of 76 out of 143 cited papers were published in the last 5 years (2019–2024). Older papers were mainly used to describe the development of synthetic photosensitizers over the years and for the introduction of PS generations. The article selection was based on title, abstract, language (English and Polish), and availability. Duplicate records were removed. The review discusses the application of PDT in cancer therapy, focusing on advances in the creation of novel photosensitizers. The review is based on research from PubMed and Google Scholar on the use of PDT in cancer treatment, with a focus on the role of synthetic photosensitizers. The collected articles were published between 1984 and 2024. A total of 76 out of 143 cited papers were published in the last 5 years (2019–2024). Older papers were mainly used to describe the development of synthetic photosensitizers over the years and for the introduction of PS generations. The article selection was based on title, abstract, language (English and Polish), and availability. Duplicate records were removed. The review includes general information about PDT and the division into the most important groups ofPhotodynamic therapy (PDT) is a promising cancer treatment that uses photosensitizing (PS) compounds to selectively destroy tumor cells using laser light. This review discusses the main advantages of PDT, such as its low invasiveness, minimal systemic toxicity, and low risk of complications. Special attention is paid to photosensitizers obtained by chemical synthesis. Three generations of photosensitizers are presented, starting with the first generation based on porphyrins, through the second generation including modified porphyrins, chlorins, 5-aminolevulinic acid (ALA), and its derivative hexyl aminolevulinate (HAL), to the third generation, which uses nanotechnology to increase therapy selectivity. Current research trends include the search for new photosensitizers that can overcome the limitations of existing therapies, such as heavy-atom-free nonporphyrinoid photosensitizers, antibody–drug conjugates (ADCs), or photosensitizers with a near-infrared (NIR) absorption peak. The review highlights the development of PDT, considering advances in nanotechnology and biomedical engineering. The references include both older and newer works. The article includes reviews and research articles, as well as case reports. The keywords are PDT and synthetic photosensitizers. The review discusses the application of PDT in cancer therapy, focusing on advances in the creation of novel photosensitizers. The review is based on research from PubMed and Google Scholar on the use of PDT in cancer treatment, with a focus on the role of synthetic photosensitizers. The collected articles were published between 1984 and 2024. A total of 76 out of 143 cited papers were published in the last 5 years (2019–2024). Older papers were mainly used to describe the development of synthetic photosensitizers over the years and for the introduction of PS generations. The article selection was based on title, abstract, language (English and Polish), and availability. Duplicate records were removed. The review discusses the application of PDT in cancer therapy, focusing on advances in the creation of novel photosensitizers. The review is based on research from PubMed and Google Scholar on the use of PDT in cancer treatment, with a focus on the role of synthetic photosensitizers. The collected articles were published between 1984 and 2024. A total of 76 out of 143 cited papers were published in the last 5 years (2019–2024). Older papers were mainly used to describe the development of synthetic photosensitizers over the years and for the introduction of PS generations. The article selection was based on title, abstract, language (English and Polish), and availability. Duplicate records were removed. The review includes general information about PDT and the division into the most important groups of