Approximately one-third of Americans struggle with an anxiety disorder, and despite the plethora of medications indicated for treatment of anxiety disorders, not all patients experience symptom relief. The heterogeneity of response to currently available treatments has spurred further research into the pathophysiology of anxiety disorders. Sonic hedgehog (SHH) signaling pathway consists of its ligand (SHH protein) and transmembrane receptors PTCH and SMO and is known to be involved in embryonic development and tissue homeostasis. Recent research has begun investigating the role of SHH in mood regulation and neuropsychiatric illnesses. In addition to a summary of the SHH molecular cascade, this chapter will focus on SHH expression in both developing and adult brain regions associated with anxiety disorders and adult neurogenesis but most importantly highlight the potential therapeutic implications for SHH signaling in treating anxiety disorders.