The vasoactive intestinal peptide (VIP) signaling axis constitutes VIP and its two G protein coupled receptors (GPCR) termed vasoactive intestinal/pituitary adenylate cyclase activating polypeptide (VPAC) 1 and 2. This signaling axis regulates numerous biological actions within the endocrine system, the nervous system and the immune system. Working as a gut hormone, VIP can increase cAMP signaling within beta-islet cells of the pancreas to impact insulin production. As a neurotransmitter, it acts as a master circadian regulator controlling light and dark cycling. Lastly, VIP regulates immune processes such as activation, chemotaxis, development and cytokine secretion. The focus of my doctoral research was to delineate VIP signaling mechanisms controlling immunity. We aimed at understanding: 1.) the molecular mechanism of VIP-induced T cell trafficking 2.) ability for VPAC2 signaling to regulate immune homeostasis and 3.) a phenotype of a B cell subset during asthma, an immune pathology devoid of VIP protein due to excessive protease activity. Methods employed utilized isolated primary mouse immune cells to measure a VIP-induced signaling pathway centered on the epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, by qPCR and chemotaxis assays. Flow cytometry to enumerate immune cell numbers in VPAC2 deficient mice was done to accomplish aim 2. Lastly, using a published in vivo allergic asthma mouse model, we used qPCR, immunoblotting and flow cytometry analyses to measure expression of Hyaluronic acid binding proteins on B cells. Results from these studies revealed that VIP signaling in T cells is regulated by EGFR as inhibitors against its enzymatic activity abolished T cell movement towards VIP. Immune cell numbers were lowered as a consequence of VPAC2 deficiency, suggesting its involvement in homeostasis. Lastly, a unique B cell population homing to asthmatic lung secretes an anti-inflammatory mediator, TGF-beta, through the HA binding protein called RHAMM. Collectively, these data emphasize the importance of VIP signaling in the immune system controlling cell migration and homeostasis.