Proper attachment to the extracellular matrix is essential for cell survival. Detachment from the extracellular matrix results in an apoptotic process termed anoikis. Anoikis induction in MCF-10A mammary epithelial cells is due not only to loss of survival signals following integrin disengagement, but also to consequent downregulation of epidermal growth factor (EGFR) and loss of EGFR-induced survival signals. Here we demonstrate that G₁/S arrest by overexpression of the cyclin-dependent kinase inhibitors p16^INK4a, p21^Cip1, or p27^Kip1 or by treatment with mimosine or aphidicolin confers anoikis resistance in MCF-10A cells. G₁/S arrest-mediated anoikis resistance involves suppression of the BH3-only protein Bim. Furthermore, in G₁/S-arrested cells, Erk phosphorylation is maintained in suspension and is necessary for Bim suppression. Following G₁/S arrest, known proteins upstream of Erk, including Raf and Mek, are not activated. However, retained Erk activation under conditions in which Raf and Mek activation is lost is observed, suggesting that G₁/S arrest acts at the level of Erk dephosphorylation. Thus, anoikis resistance by G₁/S arrest is mediated by a mechanism involving Bim suppression through maintenance of Erk activation. These results provide a novel link between cell cycle arrest and survival, and this mechanism could contribute to the survival of nonreplicating, dormant tumor cells that avert apoptosis during early stages of metastasis.