Latrophilins (LPHNs) are adhesion GPCRs that are originally discovered as spider’s toxin receptors, but are now known to be involved in brain development and linked to several neuronal and non-neuronal disorders. Latrophilins act in conjunction with other cell adhesion molecules and may play a leading role in its network organization. Here, we focus on the main protein partners of latrophilins, namely teneurins, FLRTs and contactins and summarize their respective temporal and spatial expression patterns, links to neurodevelopmental disorders as well as their structural characteristics. We discuss how more recent insights into the separate cell biological functions of these proteins shed light on the central role of latrophilins in this network. We postulate that latrophilins control the refinement of synaptic properties of specific subtypes of neurons, requiring discrete combinations of proteins.