It is well known that upregulation of Ras activity can promote cell-cycle progression. Now recent studies indicate that a reciprocal relationship also exists; that is, the consequences of Ras signaling are dependent upon cell-cycle position. In quiescent cells stimulated with growth factors, one Ras effector, phosphatidylinositol-3-kinase, is activated twice as cells transition from G(0) into G(1) phase, and then later in G(1) phase. It is only during the later stages of G(1) phase that PI3K activity promotes entry into S-phase. In cycling cells, Ras activity is enhanced throughout the cell cycle, but is able to stimulate cyclin D1 elevation only during G(2) phase.