RhoB is a mainly endosomal small GTPase that regulates actin organization and vesicle trafficking. Expression of RhoB is elevated rapidly by many stimuli, including growth factors, cytokines, and genotoxic stress. In cancer, RhoB can limit cell proliferation, survival, invasion, and metastasis, and during malignant progression its levels are attenuated commonly. In support of its role as a negative modifier of cancer progression, targeted deletion of RhoB in mice can increase tumor formation initiated by Ras mutation. How RhoB acts to suppress different aspects of cancer pathophysiology has emerged as a question of significant interest.