We have used different structural biology tools to characterize the atomic structure of the cannabinoid receptor CB1. Structures of this GPCR in the inactive conformation have revealed the molecular basis for binding and inhibition by inverse agonists and negative allosteric modulators. Comparison to structures in the active conformation show how CB1 responds to agonists to activate G protein signaling. This atomic view of the mechanism of CB1 is a useful framework for drug design and characterization.