The most important regulators of brown adipose tissue (BAT) activity include members of the G protein-coupled receptors (GPCRs) that may signal via Gs, Gq or other G proteins. Regulators of G Protein Signaling (RGS) are important modulators of GPCR activity. Klepac and colleagues elucidated the role of RGS2 in brown adipocyte differentiation and BAT function. RGS2-deficient (RGS2-/-) brown adipocytes exhibited a severe defect in adipogenesis that was caused by increased Gq signaling. Analysis of RGS2-/- mice revealed an unexpected increase in lipolysis and BAT activity due to increased Gs signaling. Thus, RGS2 is a multifunctional inhibitor of Gq that also regulates Gs signaling in BAT.