A growing body of literature suggests that comorbid anxiety disorders are more common and more prognostically relevant among migraine sufferers than comorbid depression. Panic disorder (PD) appears to be more strongly associated with migraine than most other anxiety disorders. PD and migraine are both chronic diseases with episodic manifestations, involving significant functional impairment and shared symptoms during attacks, interictal anxiety concerning future attacks, and an absence of identifiable secondary pathology. A meta-analysis of high-quality epidemiologic study data from 1990 to 2012 indicates that the odds of PD are 3.76 times greater among individuals with migraine than those without. This association remains significant even after controlling for demographic variables and comorbid depression. Other less-rigorous community and clinical studies confirm these findings. The highest rates of PD are found among migraine with aura patients and those presenting to specialty clinics. Presence of PD is associated with greater negative impact of migraine, including more frequent attacks, increased disability, and risk for chronification and medication overuse. The mechanisms underlying this common comorbidity are poorly understood, but both pathophysiological (eg, serotonergic dysfunction, hormonal influences, dysregulation of the hypothalamic–pituitary–adrenal axis) and psychological (eg, interoceptive conditioning, fear of pain, anxiety sensitivity, avoidance behavior) factors are implicated. Means of assessing comorbid PD among treatment-seeking migraineurs are reviewed, including verbal screening for core PD symptoms, ruling out medical conditions with panic-like features, and administering validated self-report measures. Finally, evidence-based strategies for both pharmacologic and behavioral management are outlined. The first-line migraine prophylactics are not indicated for PD, and the selective serotonin re-uptake inhibitors used to treat PD are not efficacious for migraine; thus, separate agents are often required to address each condition. Core components of behavioral treatments for PD are reviewed, and their integration into clinical headache practice is discussed.