The polyamines spermidine (1,8-diamino-4-azaoctane, 2) and spermine (1,12-diamino-4,9-diazadodecane, 3), as well as the precursor molecule putrescine (1,4-diaminobutane, 1), are polycationic compounds which are found in significant amounts in nearly every prokaryotic and eukaryotic cell type. Despite the ubiquitous nature of these compounds, the precise roles that polyamines play in cellular physiology are still being defined, with new avenues for research arising continuously. As a result, there are active research programs focusing on polyamine metabolism in an extremely diverse set of disciplines. The pathways for polyamine metabolism have been elucidated for a relatively small number of organisms. There are important interspecies differences in polyamine metabolism, especially between eukaryotic cells, plants, and some bacteria and protozoa. In some parasitic organisms, there are additional enzymes which are not present in the host cell and, as such, provide a target for the design of specific antiparasitic agents. However, the enzymes involved in human and mammalian polyamine metabolism are reasonably similar, and inhibitors targeted to these enzymes rely on the observation that polyamine metabolism is accelerated and polyamines are required in higher quantities, in target cell types. The diversity of biological research in the polyamine field is the subject of an excellent book by Seymour Cohen. This Perspective will deal with the use of polyamine analogues as chemotherapeutic agents, i.e., the use of synthetic polyamine analogues as anticancer or antiinfective agents. The reader should be aware of additional areas of polyamine research (polyamines as modulators of the NMDA receptor, polyamine-based venoms, polyamines as potential carriers for drug delivery, polyamines used in boron-neutron capture therapy, etc.) which are beyond the scope of this review. The polyamine pathway represents an important target for chemotherapeutic intervention, since depletion of polyamines results in the disruption of a variety of cellular functions and may in specific cases result in cytotoxicity. Inhibitors of the polyamine pathway, therefore, have traditionally been developed as potential antitumor and/or antiparasitic agents. Such inhibitors also play a critical role as research tools to elucidate the cellular functions of the naturally occurring polyamines, especially if these agents are specific for a single enzyme in the pathway. Inhibitors have now been developed for the enzymes in the polyamine biosynthetic pathway, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMet-DC), and for the aminopropyltransferases spermidine synthase and spermine synthase. The interruption of the polyamine metabolic pathway by these inhibitors leads to a variety of responses ranging from cessation of cell growth to overt cytotoxicity. The range of these activities appears to be both agent- and cell-type-specific. On the basis of this knowledge, we and others have focused on the development of agents which interfere with the polyamine pathway as a means of antineoplastic and antiparasitic intervention.