Advanced heart failure (AHF) is not a uniform disorder, but is rather a heterogeneous group of patients with varying clinical presentations and definitions. It is growing in magnitude and represents a major public health problem. Herein we describe contemporary care of the patient with AHF, novel medical therapies, and mechanical circulatory assist devices. We speculate where progress has been made and where the major gaps in knowledge remain. Clearly, there is ample opportunity for research and discovery to further advance the care of these very sick patients.