The polyamines are small basic molecules essential for cellular proliferation and viability. An autoregulatory circuit that responds to the intracellular level of polyamines regulates their production. In the center of this circuit is a family of small proteins termed antizymes. Antizymes are themselves regulated at the translational level by the level of polyamines. Antizymes bind ornithine decarboxylase (ODC) subunits and target them to ubiquitin-independent degradation by the 26S proteasome. In addition, antizymes inhibit polyamine transport across the plasma membrane via an as yet unresolved mechanism. Antizymes may also interact with and target degradation of other growth-regulating proteins. An inactive ODC-related protein termed antizyme inhibitor regulates polyamine metabolism by negating antizyme functions. The ability of antizymes to degrade ODC, inhibit polyamine uptake and consequently suppress cellular proliferation suggests that they act as tumor suppressors, while the ability of antizyme inhibitors to negate antizyme function indicates their growth-promoting and oncogenic potential.