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Synopsis Lizards use chemical communication to mediate many reproductive, competitive, and social behaviors, but the neuroendocrine mechanisms underlying chemical communication in lizards are not well understood and understudied. By implementing a neuroendocrine approach to the study of chemical communication in reptiles, we can address a major gap in our knowledge of the evolutionary mechanisms shaping chemical communication in vertebrates. The neuropeptide arginine vasotocin (AVT) and its mammalian homolog vasopressin are responsible for a broad spectrum of diversity in competitive and reproductive strategies in many vertebrates, mediating social behavior through the chemosensory modality. In this review, we posit that, though limited, the available data on AVT-mediated chemical communication in lizards reveal intriguing patterns that suggest AVT plays a more prominent role in lizard chemosensory behavior than previously appreciated. We argue that these results warrant more research into the mechanisms used by AVT to modify the performance of chemosensory behavior and responses to conspecific chemical signals. We first provide a broad overview of the known social functions of chemical signals in lizards, the glandular sources of chemical signal production in lizards (e.g., epidermal secretory glands), and the chemosensory detection methods and mechanisms used by lizards. Then, we review the locations of vasotocinergic populations and neuronal projections in lizard brains, as well as sites of peripheral receptors for AVT in lizards. Finally, we end with a case study in green anoles (Anolis carolinensis), discussing findings from recently published work on the impact of AVT in adult males on chemosensory communication during social interactions, adding new data from a similar study in which we tested the impact of AVT on chemosensory behavior of adult females. We offer concluding remarks on addressing several fundamental questions regarding the role of AVT in chemosensory communication and social behavior in lizards.