Farnesyltransferase inhibitors (FTIs) usually cause growth inhibition, but in certain preclinical settings they have been shown to induce apoptosis, a clinically desirable response. In this study, we show that the proapoptotic effects of FTIs in Ras-transformed cells are masked by activation of phosphatidylinositol 3′-kinase (PI3′K) or AKT, which are controlled by cytokines and integrins. The results implied that FTIs disrupt a signal that is crucial for survival of malignant cells, but not normal cells, if the PI3′K-AKT pathway is inactivated. Our findings have implications for clinical applications of FTIs where apoptotic responses would be preferred.