Advanced systolic heart failure refractory to ambulatory pharmacotherapy continues to be a clinical dilemma with increasing incidence and prevalence. By establishing the presence of signs and symptoms, clinicians could better evaluate hemodynamic perturbations, therefore targeting them through the use of intravenous diuretics, intravenous vasodilators, and intravenous inotropic therapy. This review focuses on the unique features that characterize advanced heart failure, and discusses the special clinical considerations in managing this morbid entity.