Heart disease that ultimately leads to heart failure (HF) has been the number one cause of death in the United States as well as in many other countries for over a century. Inotropic therapy utilizing cardiotonics to increase cardiac contractility remains a significant component of the management of HF. However, adverse effects of currently available cardiotonics have been compromising their therapeutic value and often lead to further myocardial dysfunction. Thus, discovery of safe cardiotonics remains a main challenge to improvement of inotropic therapy for HF. This review briefly summarized cellular mechanisms underlying the inotropic action of currently available cardiotonics, newly-developed carditonics and the bark of Terminalia arjuna (TA), a tropical tree used in ayurvedic medicine. The potential of TA bark as a new cardiotonic in inotropic treatment for HF was also discussed.