Although cardiac glycosides have been used clinically for the treatment of heart failore for over 200 yr not used the 1920s was it appreciated that these drugs increased the force of contraction of heart muscle, providing a plaesible mechanism of action for their therapeutic effect in patients with heart failure. The drugs in this class are selective inhibitors of the integral plasma membrane enzyme Nak-ATPase the “sodium pump” that is responsible for maintaining many of the ion gradients necessary for normal cellular function. In cardiac muscle, sodium pump inhibition indirectly leads to an increase in the cellular content of calcium and increased calcium access to the contractile elements during excitation-contraction coupling, resulting in greather force generation. The net effect in patients with heart failure is to increase stroke output at a given level of ventricular-filling pressure resulting in an increase in cardiac output and a decrease in ventricular-filling pressure and congestive symptoms. Cardiac glycosides also increase baroreflex sensitivily probably by a direct action on neural sensing cells in low and high pressure baroreceptors. This increased sensitivity results in a decline in sympathetic nervous system activation and an increase in parasympathetic nervous system activation that facilitates a decline in heart rate, slowing AV nodal conduction and decreasing both peripheral vascular resistance and salt and water retention.