Over the forty years since its discovery, there has been a profound transition in thinking with regard to the role of troponin in the control of cardiac function. This transition involved a change in perception of troponin as a passive molecular switch responding to membrane controlled fluctuations in cytoplasmic Ca2+ to a perception of troponin as a critical element in signaling cascades that actively engage in control of cardiac function. Evidence demonstrating functionally significant developmental and mutant isoform switches and post-translational modifications of cardiac troponin complex proteins, troponin I (cTnI) and troponin T (cTnT) provided convincing evidence for a more complicated role of troponin in control of cardiac function and dynamics. The physiological role of these modifications of troponin is reviewed in this monograph and has also been reviewed elsewhere (Solaro and Rarick, 1998; Gordon et al., 2000; Solaro et al., 2002a; Kobayashi and Solaro, 2005). Our focus here is on studies related to modifications in troponin that appear important in the processes leading from compensated hypertrophy to heart failure. These studies reveal the potentially significant role of post-translational modifications of troponin in these processes. Another focus is on troponin as a target for inotropic agents. Pharmacological manipulation of troponin by small molecules remains an important avenue of approach for the treatment of acute and chronic heart failure (Kass and Solaro, 2006).