Polyamines, essential for cell growth and function, interact with various macromolecules and play a crucial role in maintaining cellular homeostasis. Their metabolism is complex, involving multiple regulatory mechanisms to ensure optimal levels. Key enzymes in polyamine metabolism include ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SSAT), and polyamine oxidase (PAO). These enzymes are regulated at various levels, including transcription, translation, and post-translational modifications. Polyamines can also be transported into and out of cells, with transporters playing a role in maintaining intracellular levels. The regulation of polyamine metabolism is tightly controlled, and deviations from normal levels can lead to cell growth arrest, transformation, or cell death. In cancer, increased polyamine content is often observed, and inhibitors of polyamine biosynthesis, such as α-fluoromethylornithine (DFMO), have shown limited success in cancer treatment due to compensatory mechanisms. However, DFMO has found success in treating parasitic infections. Recent developments in polyamine analogues aim to overcome these limitations by targeting multiple steps in the polyamine pathway, potentially providing more effective chemopreventive and therapeutic agents. The future of polyamine research may involve using functional genomics to identify genes regulated by polyamines, further advancing our understanding of their role in cellular processes.Polyamines, essential for cell growth and function, interact with various macromolecules and play a crucial role in maintaining cellular homeostasis. Their metabolism is complex, involving multiple regulatory mechanisms to ensure optimal levels. Key enzymes in polyamine metabolism include ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SSAT), and polyamine oxidase (PAO). These enzymes are regulated at various levels, including transcription, translation, and post-translational modifications. Polyamines can also be transported into and out of cells, with transporters playing a role in maintaining intracellular levels. The regulation of polyamine metabolism is tightly controlled, and deviations from normal levels can lead to cell growth arrest, transformation, or cell death. In cancer, increased polyamine content is often observed, and inhibitors of polyamine biosynthesis, such as α-fluoromethylornithine (DFMO), have shown limited success in cancer treatment due to compensatory mechanisms. However, DFMO has found success in treating parasitic infections. Recent developments in polyamine analogues aim to overcome these limitations by targeting multiple steps in the polyamine pathway, potentially providing more effective chemopreventive and therapeutic agents. The future of polyamine research may involve using functional genomics to identify genes regulated by polyamines, further advancing our understanding of their role in cellular processes.