Patent foramen ovale (PFO) may be an underlying factor in the pathogenesis of migraine, vasospastic angina, and Takotsubo cardiomyopathy. This article reviews the role that PFO may play in each of these clinical entities and discusses potential interventions. It also proposes a novel clinical syndrome wherein PFO may be the unifying link among migraine, coronary vasospasm, and Takotsubo cardiomyopathy in predisposed individuals.