Adhesion family of G Protein-Coupled Receptors are cell surface receptors that mediate cellular communication and play critical roles in numerous physiological functions that range from embryonic and neural development. However, their mechanisms of action remain poorly understood. In the past several years, three-dimensional structures of several adhesion GPCRs have been reported at atomic resolutions and revealed distinct protein folds and unique structural features. In this presentation, we will discuss these structures which, together with structure-guided biochemical and functional analyses, provide hints for the mechanisms of trans-cellular communication at the synapse and other cell-cell contact sites.