The article discusses the role of serine, glycine, and one-carbon metabolism in cancer pathogenesis. One-carbon metabolism, which integrates carbon units from amino acids like serine and glycine, plays a crucial role in various cellular processes such as lipid, nucleotide, and protein biosynthesis, redox status maintenance, and methylation reactions. Recent studies have revealed that hyperactivation of this pathway can be a driver of oncogenesis and is linked to cellular epigenetic status. The review highlights the clinical significance of targeting one-carbon metabolism in cancer therapy, including the use of drugs like methotrexate and pemetrexed, as well as the potential of metformin and dietary interventions. It also explores the complex interactions between one-carbon metabolism and other biological pathways, such as protein translation, genome maintenance, and epigenetic alterations. The article concludes by emphasizing the potential for precision medicine and biomarker discovery in cancer treatment, leveraging the newly understood roles of one-carbon metabolism in cancer pathogenesis.The article discusses the role of serine, glycine, and one-carbon metabolism in cancer pathogenesis. One-carbon metabolism, which integrates carbon units from amino acids like serine and glycine, plays a crucial role in various cellular processes such as lipid, nucleotide, and protein biosynthesis, redox status maintenance, and methylation reactions. Recent studies have revealed that hyperactivation of this pathway can be a driver of oncogenesis and is linked to cellular epigenetic status. The review highlights the clinical significance of targeting one-carbon metabolism in cancer therapy, including the use of drugs like methotrexate and pemetrexed, as well as the potential of metformin and dietary interventions. It also explores the complex interactions between one-carbon metabolism and other biological pathways, such as protein translation, genome maintenance, and epigenetic alterations. The article concludes by emphasizing the potential for precision medicine and biomarker discovery in cancer treatment, leveraging the newly understood roles of one-carbon metabolism in cancer pathogenesis.