Flavonoids are integral components of various vegetation and in foods; consequently, they represent an inevitable part of the diet. Historical and epidemiological proof recommend that diet plans consisting of flavonoids such as quercetin have positive health benefits, especially on the heart. Flavonoids have been proven to be active against hypertension, inflammation, diabetes and vascular diseases. Quercetin exhibits significant heart related benefits as inhibition of LDL oxidation, endothelium-independent vasodilator effects, reduction of adhesion molecules and other inflammatory markers, the protective effect on nitric oxide and endothelial function under conditions of oxidative stress, prevention of neuronal oxidative and inflammatory damage and platelet antiaggregant effects. Searching for experimental evidence to validate the cardioprotective effects of quercetin, we review here the recent detailed in vivo studies. Quercetin and its derivatives lead to an enhancement in heart features, indicating the prospective for quercetin to be used therapeutically in the treatment of cardiac diseases. Several evidence based studies suggest mechanisms to observe cardiovascular diseases such as aging effects, hypertension,angiotensin-converting enzyme activity and endothelial-dependent and independent functions. Different animal models including human are also used to elucidate the in vivo role of quercetin in cardiovascular diseases. The role of quercetin and its derivatives may go beyond their existence in food and has potential as a lead molecule in drug development programs.