Diabetes results in a cardiomyopathy characterized by reduced contractility that is primarily the result of changes in calcium handling within the myocyte. Because most of the calcium involved in excitation-contraction (EC) coupling is derived from the sarcoplasmic reticulum (SR), it is no surprise that many studies have found a reduction in sarco-endoplasmic reticulum calcium ATPase (SERCA) activity in the diabetic state. In this review, we outline the changes to SR calcium handling in the diabetic state and, through the use of transgenic mice and adenoviral gene therapy, we examine how SR function can be improved by the expression of various proteins that are directly and indirectly involved in calcium handling. Improving SERCA activity plays an important role in ameliorating the contractile phenotype associated with the diabetic state.