The regulators of G protein signaling (RGS) are an extraordinary class of diverse multifunctional signaling proteins best known for their potent capacity to down-regulate the activity of Galpha subunits at the plasma membrane. In certain circumstances, some RGS proteins undergo translocation to the nucleus or plasma membrane from the cytoplasm. Translocation demonstrates a potentially dynamic alternative mechanism for Galpha subunit or effector regulation. The nuclear localization of the regulators of G protein signaling proteins further suggests these proteins possess even greater functional heterogeneity than that envisioned previously, as regulators of transcription and cell cycle control.