When a resting cell is awakened to enter the cell cycle by mitogenic stimulation, a complex molecular machinery involving positive and negative regulation of cell-cycle progression is initiated. Part of the machinery is quite well-known. It involves receptors of various kinds, protein interactions, phosphorylation reactions, and molecular cascades carrying the signal to enter the cell cycle from the cell surface to the nucleus. In the nucleus, transcriptional activation results in an increased involvement of genes in the process. In the cytoplasm, translational and posttranslational mechanisms also have a part in the process. In this complex partly known molecular machinery, there are also molecules that not yet have been assigned a specific role; however, there are enough data to state that their role in normal cell-cycle progression is ubiquitous. The level of the polyamines—putrescine, spermidine, and spermine—are low in nonproliferating cells, but their levels increase early after mitogenic stimulation and these increases are necessary for normal rates of cell-cycle progression (1,2). In this chapter, the focus will be on the role of polyamines in early signaling processes that are required for normal cell-cycle progression.