Cardiovascular disease remains a leading cause of hospitalization and mortality worldwide. Conventional heart failure treatment is making steady and substantial progress to reduce the burden of disease. Nevertheless novel therapies and especially cardiac gene therapy have been emerging in the past and successfully made their way into first clinical trials. Gene therapy was initially a visionary treatment strategy for inherited, monogenetic diseases but has now developed to have potential for polygenic diseases as atherosclerosis, arrhythmias and heart failure. These novel therapeutic strategies require testing in clinically relevant animal models to transition from ‘bench to bedside’. One of the major hurdles for effective cardiovascular gene therapy is the delivery of the viral vectors to the heart. In this review we present the currently available vector-mediated cardiac gene delivery methods in vivo considering the specific merits and deficiencies.