This chapter aims to cover discussion on cardiac glycosides and treatment of cardiac failure. Myocardium is made up of two types of cells i.e. contracting cells and conducting cells. Automaticity is the ability of cells to generate electrical impulses spontaneously and present in sinoatrial (SA) node, atrioventricular (AV) node, Purkinje fibers, bundle of His. Congestive cardiac failure (CCF) is the inability of heart to provide adequate blood supply to meet body’s oxygen demand. In patients of CCF, the contracting ability of ventricles is decreased. There are two types of cardiac failure. First is low output due to ischemic heart disease, hypertension, valvular heart disease and second is high output due to thyrotoxicosis, anemia, beriberi, congenital heart disease. A detailed description on cardiac glycosides and drugs for congestive cardiac failure has been also covered in this chapter.