Mast cells generated from Rac2-deficient (−/−) mice demonstrated defective actin-based functions, including adhesion, migration, and degranulation. Rac2^−/− mast cells generated lower numbers and less mast cell colonies in response to growth factors and were deficient in vivo. Rac2^−/− mast cells demonstrated a significant reduction in growth factor–induced survival, which correlated with the lack of activation of Akt and significant changes in the expression of the Bcl-2 family members BAD and Bcl-X_L, in spite of a 3-fold induction of Rac1 protein. These results suggest that Rac2 plays a unique role in multiple cellular functions and describe an essential role for Rac2 in growth factor–dependent survival and expression of BAD/Bcl-X_L.