Cardiovascular diseases pose a unique threat to global mortality because it presents as one of the most diverse conglomerations of pathophysiological conditions that can create significant casualty even without straying into its collateral damage. This puts them right beside obesity and cancer in terms of severity. Their pervasive nature and high prevalence prompted biologists to seek newer prophylactic avenues of addressing this global hazard, among which adeno-associated virus (AAV) gene therapy rose to significant prominence. By virtue of its unrivaled clinical safety quotient, AAVs have been used to rectify various subtypes of cardiovascular ailments, beginning from commonly occurring heart failure to vascular diseases. The review focuses on the history of AAV-mediated gene therapy and contemporary breakthroughs in terms of novel innovations in vector engineering to reduce detargeting, immune response, untimely expression, and so on. We have also focused on the molecular world of cardiomyocytes and endothelial cells but interpreted the therapies in a broader context of cardiovascular pathology. The advances made in each mode of intervention as well as the ones that are beyond the scope of AAV gene therapy or has not been approached through AAV gene therapy as of now have been provided in detail to illustrate the bigger picture of where we stand to combat cardiovascular diseases most efficiently.