Despite the number of available methods to predict prognosis in patients with heart failure, prognosis remains poor, likely because of marked patient heterogeneity and varied heart failure etiologies. Thus, identification of novel prognostic indicators to stratify risk in patients with heart failure is of paramount importance. The spleen is emerging as a potential novel prognostic indicator for heart failure. In this article, we provide an overview of the current prognostic tools used for heart failure. We then introduce the spleen as a potential novel prognostic indicator, before outlining the structure and function of the spleen and introducing the concept of the cardiosplenic axis. This is followed by a focused discussion on the function of the spleen in the immune response and in hemodynamics, as well as a review of what is known about the usefulness of the spleen as an indicator of heart failure. Expert insight into the most effective spleen-related measurement indices for the prognostication of patients with heart failure is provided, and suggestions on how these could be measured in clinical practice are considered. In future, studies in humans will be required to draw definitive links between specific splenic measurements and different heart failure manifestations, as well as to determine whether splenic prognostic measurements differ between heart failure classes and etiologies. These contributions will provide a step forward in our understanding of the usefulness of the spleen as a prognostic predictor in heart failure.