The Vav family of proteins are guanine nucleotide exchange factors which have been shown to be deregulated in several types of human cancer. There are three members of the Vav family that have been identified which are members of the Dbl domain superfamily and have specificity towards Rho/Rac GTPases. The Vav family plays an important role in normal hematologic system development and homeostasis, and Vav1 is largely restricted to the hematologic system. While Vav1 was originally identified as a proto-oncogene, several recent studies have shown that Vav family deletion leads to the development of T-cell malignancies in mice. In addition, Vav1 has been shown to play a role in the ATRA-mediated differentiation of promyelocytic leukemia cells. In this concise review, the gene structure and normal function of Vav1, as well as a possible role for Vav1 in the development of hematologic and other malignancies is reviewed.