Since their initial discovery in yeast, cyclin-dependent kinases have proven to be universal regulators of the cell cycle in all eukaryotes. In unicellular eukaryotes, cell cycle progression is principally governed by one catalytic subunit (cyclin-dependent kinase) that pairs with cell cycle-specific regulatory subunits known as cyclins. Progression through a specific phase of the cell cycle is under the control of a specific class of cyclin. Cell cycle control in multicellular eukaryotes has an additional layer of complexity, as multiple CDKs and cyclins are required. In this review, we will discuss recent advances in the area of cyclins and CDKs, with emphasis on the role of the mammalian proteins in cell cycle control at the cellular and at the organismal level. Many recent surprises have come to light recently as a result of genetic manipulation of cells and mice, and these findings suggest that our understanding of the intricacies of the cell cycle is still rudimentary at best.