Apical ballooning syndrome (ABS) describes acute regional myocardial dysfunction and has a strong association with emotional stress and female sex. Whilst catecholamine excess has been described in this condition, the precise etiology remains elusive. We report the atypical case of a 61 year old male who developed ABS in the absence of a clear precipitant. His concurrent treatment with a vascular endothelial growth factor (VEGF) receptor antagonist may provide an insight into the pathogenesis of this enigmatic condition. We present a biologically plausible explanation as to why VEGF antagonism may have an important role through its modulation of nitric oxide and catecholamine effects. This hypothesis may also provide an important insight into the cardiovascular toxicities associated with this class of drug. In addition, we report the success of treatment with a beta blocker in ABS complicated by a severe left ventricular outflow tract obstruction.