The three subtypes of beta-adrenergic receptor (beta AR) all interact with G proteins as a central aspect of their signaling. The various beta AR subtypes also associate differentially with a variety of other cytoplasmic and transmembrane proteins. These beta AR-interacting proteins play distinct roles in the regulation of receptor signaling and trafficking. The specificity of beta AR associations with various binding partners can help to explain key physiological differences between beta AR subtypes. Moreover, the differential tissue expression patterns of many of the beta AR-interacting proteins may contribute to tissue-specific regulation of beta AR function.