Vav proteins (Vav1, Vav2, and Vav3) function as guanosine nucleotide exchange factors (GEFs) for the Rho/Rac family proteins. As a member of Vav family proteins, Vav3 contains multiple domains that enable its function in various fashions by activating different Rho GTPases. It couples cell surface receptors to various effectors and modulates multiple signaling pathways including MAPK, PI3K-Akt and NF-κB. Vav3 plays a pivotal role in the maintenance of cell shape, cell adhesion, angiogenesis, regulation of immunity and cell differentiation. Recent studies indicated that the deregulated expression of Vav3 is often linked to tumorigenicity. This suggested that Vav3 can work as a proto-oncogene. The scope of this review is to highlight the structure and numerous roles of the Vav3 and its related signal pathways.