Background?Cognitive–behavioural theories of panic disorder posit that panic attacks arise from a positive feedback loop between arousal-related bodily sensations and perceived threat. In a recently developed computational model formalising these theories of panic attacks, it was observed that the response to a simulated perturbation to arousal provided a strong indicator of vulnerability to panic attacks and panic disorder. In this review, we evaluate whether this observation is borne out in the empirical literature that has examined responses to biological challenge (eg, CO2 inhalation) and their relation to subsequent panic attacks and panic disorder. Method?We searched PubMed, Web of Science and PsyclNFO using keywords denoting provocation agents (eg, sodium lactate) and procedures (eg, infusion) combined with keywords relevant to panic disorder (eg, panic). Articles were eligible if they used response to a biological challenge paradigm to prospectively predict panic attacks or panic disorder. Results?We identified four eligible studies. Pooled effect sizes suggest that there is biological challenge response has a moderate prospective association with subsequent panic attacks, but no prospective relationship with panic disorder. Conclusions?These findings provide support for the prediction derived from cognitive–behavioural theories and some preliminary evidence that response to a biological challenge may have clinical utility as a marker of vulnerability to panic attacks pending further research and development. Trial registration number?135908.