The Rho family of GTPases have emerged as key players in regulating a diverse set of biological activities including actin organization, focal complex/adhesion assembly, cell motility, cell polarity, gene transcription and cell-cycle progression. Some Rho GTPases and their signaling components are overexpressed and/or are hyperactive in breast cancer and recent studies have shown a requirement for Rho GTPases in breast cancer cell metastasis in vivo. Herein we describe the contribution of Rho GTPase to the malignant phenotype of breast cancer cells and the role of these pathways as potential targets for breast cancer therapy. Rho GTPases promote cell-cycle progression through cyclin D1, and cyclin D1 in turn reduces cellular adhesion and promotes migration, an example of ‘inside-out’ signaling by cyclin D1. As cyclin D1 overexpression correlates with metastatic cancer, the ‘inside-out’ signaling function of cyclin D1 to promote cell migration may represent a useful new therapeutic target.