Heart transplantation is currently the only viable option available for the treatment of severe heart failure conditions such as dilated cardiomyopathy. Hence, novel drugs for treating such conditions need to be developed urgently. Recent studies suggest that Ca2+ overload is involved in the onset and progression of dilated cardiomyopathy, and thus heart failure. The expression and activation of the Ca2+ permeable channel, transient receptor potential vanilloid 2 (TRPV2) channel have been found to play an essential role in sustained intracellular Ca2+ concentration increase, leading to heart failure. However, since there have been no TRPV2-specific inhibitors available until recently, the effect of TRPV2 inhibition on the pathology has not been clearly elucidated. Recent reports show that inhibiting TRPV2 activity effectively improves cardiac function, suppressing myocardial fibrosis and ameliorating the prognosis in animal models of cardiomyopathy with heart failure. In addition to that, inflammation is reported to be involved in the development of heart failure. Here, we review the recent findings on TRPV2 in cardiomyocytes and immune cells involved in the development of heart failure and discuss the current progress of drug development for the treatment of heart failure via targeting TRPV2.