The bark of the tree Terminalia arjuna (Roxb.) is widely used in Indian medicine (Ayurveda) for various cardiovascular ailments. The bark has been reported to contain several bioactive compounds. Many experimental studies have reported its antioxidant, anti-ischemic, antihypertensive, and antihypertrophic effects, which have relevance to its therapeutic potential in cardiovascular diseases in humans. Several clinical studies have reported its efficacy mostly in patients with ischemic heart disease, hypertension, and heart failure. However, a major shortcoming in all these experimental and clinical studies is the absence of phytochemical standardization of the extracts. In addition, many clinical studies are poor in terms of design and methods used for generating safety data. This review discusses how to address all these issues for a scientific validation of this medicinal plant.