Neurexins (NRXNs) have been linked to neurodevelopmental and neuropsychiatric disorders and have become attractive drug targets. They are transmembrane neuronal adhesion molecules and play important roles in the formation and differentiation of synapses and synaptic activity. Many postsynaptic binding partners of NRXNs have been identified. The interactions between NRXNs and postsynaptic binding partners can be regulated by alternative splicing, synaptic activity, and RNA binding proteins. The postsynaptic interactive partners may compete with each other for NRXN binding. The expression of NRXNs can also be regulated transcriptionally and post-transcriptionally. Genetic polymorphism may affect the function and expression of NRXNs. In this review, we will summarize the recent advance in these areas. Understanding the biology of neurexin signaling is essential for developing neurexin-based drugs.