Heart failure is a complex clinical syndrome arising from reduced cardiac contractile function and affecting a significant portion of the adult population while increasing rapidly with age. The most important cause of heart failure is systolic dysfunction which can be detected by means of non-invasive imaging. The aim of this chapter is to provide an overview of the current and emerging applications of molecular imaging techniques in heart failure. We review the current role of non-invasive imaging of myocardial ischemia and viability in the diagnostic work-up of patients with heart failure and discuss possibilities for the analysis of cardiac metabolism. Then, we present an update on molecular imaging of novel disease markers of heart failure with potential implications in prognostication and monitoring of therapy, including inflammation, neuronal dysfunction, amyloidosis, apoptosis, angiogenesis, and non-invasive imaging of cardiac gene and cell therapies.