The article reviews the significant role of plant-derived compounds in the development of clinically useful anti-cancer agents. Over 60% of currently used anti-cancer drugs are derived from natural sources, including plants, marine organisms, and microorganisms. The search for these agents began in the 1950s with the discovery of vinblastine and vincristine, followed by the isolation of cytotoxic podophyllotoxins. The National Cancer Institute (NCI) initiated a plant collection program in 1960, leading to the discovery of novel chemotypes such as taxanes and camptothecins. Despite the long history of plant use in cancer treatment, many claims are often based on folklore and traditional medicine, which may not be scientifically validated. Key plant-derived anti-cancer agents in clinical use include vinblastine, vincristine, etoposide, teniposide, paclitaxel (Taxol®), topotecan, irinotecan, homoharringtonine, and elliptinium. These agents have shown efficacy against various cancers, including leukemia, lymphoma, breast cancer, and lung cancer. Recent additions to the armamentarium include flavopiridol, combretastatin A4 phosphate, roscovitine, and pervillemes, which are in clinical or preclinical development. The article also discusses the challenges of natural products, such as limited solubility and narrow therapeutic indices, and highlights the potential of attaching these agents to monoclonal antibodies for targeted therapy. Examples include maytansine and thapsigargin, which have shown promise in clinical trials for treating specific types of cancer. Finally, the article emphasizes the importance of high-throughput screening for identifying new molecular targets, such as cyclin-dependent kinases, and the role of natural products in discovering novel inhibitors of these targets. The discovery and development of anti-cancer agents from natural sources continue to be a vital area of research, with ongoing efforts to improve their efficacy and reduce toxicity.The article reviews the significant role of plant-derived compounds in the development of clinically useful anti-cancer agents. Over 60% of currently used anti-cancer drugs are derived from natural sources, including plants, marine organisms, and microorganisms. The search for these agents began in the 1950s with the discovery of vinblastine and vincristine, followed by the isolation of cytotoxic podophyllotoxins. The National Cancer Institute (NCI) initiated a plant collection program in 1960, leading to the discovery of novel chemotypes such as taxanes and camptothecins. Despite the long history of plant use in cancer treatment, many claims are often based on folklore and traditional medicine, which may not be scientifically validated. Key plant-derived anti-cancer agents in clinical use include vinblastine, vincristine, etoposide, teniposide, paclitaxel (Taxol®), topotecan, irinotecan, homoharringtonine, and elliptinium. These agents have shown efficacy against various cancers, including leukemia, lymphoma, breast cancer, and lung cancer. Recent additions to the armamentarium include flavopiridol, combretastatin A4 phosphate, roscovitine, and pervillemes, which are in clinical or preclinical development. The article also discusses the challenges of natural products, such as limited solubility and narrow therapeutic indices, and highlights the potential of attaching these agents to monoclonal antibodies for targeted therapy. Examples include maytansine and thapsigargin, which have shown promise in clinical trials for treating specific types of cancer. Finally, the article emphasizes the importance of high-throughput screening for identifying new molecular targets, such as cyclin-dependent kinases, and the role of natural products in discovering novel inhibitors of these targets. The discovery and development of anti-cancer agents from natural sources continue to be a vital area of research, with ongoing efforts to improve their efficacy and reduce toxicity.