Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Although there are established mechanisms and preventions for CVDs, they are not totally elucidative and effective. Emerging evidence suggests that the dysregulation of ion channels in the cell membranes underpins the dysfunction of the cardiovascular system. To date, a variety of cation channels have been widely recognized as important targets for the treatment of CVDs. As a critical component of the anion channels, the volume-regulated anion channel (VRAC) is involved in a series of cell functions by the volume regulation and maintenance of membrane homeostasis. It has been confirmed to play crucial roles in cell action potential generation, cell proliferation, differentiation and apoptosis, and the VRAC appears to be a major participant in metabolic processes during CVDs. This review summarizes the current evidence and progress concerning the VRAC, to determine the future directions and challenges for CVDs for both preventive and therapeutic purposes.