Panic disorder (PD), a complex anxiety disorder characterized by recurrent panic attacks, represents a poorly understood psychiatric condition which is associated with significant morbidity and an increased risk of suicide attempts and completed suicide. Recently however, neuroimaging and panic provocation challenge studies have provided insights into the pathoetiology of panic phenomena and have begun to elucidate potential neural mechanisms that may underlie panic attacks. In this regard, accumulating evidence suggests that acidosis may be a contributing factor in induction of panic. Challenge studies in patients with PD reveal that panic attacks may be reliably provoked by agents that lead to acid-base dysbalance such as CO2 inhalation and sodium lactate infusion. Chemosensory mechanisms that translate pH into panic-relevant fear, autonomic, and respiratory responses are therefore of high relevance to the understanding of panic pathophysiology. Herein, we provide a current update on clinical and preclinical studies supporting how acid-base imbalance and diverse chemosensory mechanisms may be associated with PD and discuss future implications of these findings.