Ever since ghrelin was first discovered in 1999 as the endogenous ligand for the growth hormone secretagogue receptor, this gut-derived hormone has been implicated in a diverse range of physiological functions. Of particular interest, ghrelin has emerged as a potent modulator of the cardiovascular system, with therapeutic actions in a plethora of cardiovascular morbidities. Here, I present a series of investigations that employ a variety of experimental approaches to illuminate the pleiotropic benefits of exogenous ghrelin in treating pulmonary hypertension, acute myocardial infarction and peripheral artery disease, and highlight key mechanistic pathways that ghrelin targets to elicit its physiological effects. I will also discuss how reduced circulating levels of endogenous ghrelin may present as a unique and significant risk factor for the onset and severity of cardiovascular disease. Finally, looking forward, I consider the idea that down-regulation of the ghrelin pathway may be preferentially inherent in specific populations that are known to have a greater pre-disposition to CVD in New Zealand.