CD36, also known as scavenger receptor B2, is a multifunctional receptor widely expressed in various organs. CD36 plays a crucial role in the uptake of long-chain fatty acids, the main metabolic substrate in myocardial tissue. The maturation and transportation of CD36 was regulated by the post-translational modifications including phosphorylation, ubiquitination, glycosylation, and palmitoylation. CD36 is decreased in pathological cardiac hypertrophy caused by ischemia-reperfusion and pressure overload, while increased in diabetic cardiomyopathy. Deficiency of CD36 alleviate diabetic cardiomyopathy, while overexpression of CD36 eliminates the damage of ischemia-reperfusion, suggesting that CD36 is closely associated with the progression of cardiovascular diseases. and it is expected to be a new therapeutic target. This review summarizes the regulation and post-translational modifications of CD36, and evaluates its role in main cardiovascular diseases and its potential as a therapeutic target.