G protein coupled receptors (GPCRs) conduct the majority of transmembrane responses to hormones and neurotransmitters, and mediate the senses of sight, smell and taste. The β2 adrenergic receptor (β2AR) and the M2 muscarinic receptors are prototypical Family A GPCRs that mediate physiologic responses to autonomic nervous system activity. We have obtained three-dimensional structures of the β2AR and the M2 muscarinic receptor in inactive and active conformations, as well as a structure of the β2AR in complex with the G protein Gs. We have also used fluorescence, EPR and NMR spectroscopy to study the dynamic properties of the β2AR, and to map ligand-specific conformational changes. I will discuss what these studies have taught us about allosteric regulation of GPCR structure by G proteins and ligands.