Preload reserve represents an important concept in the normal physiologic responses of the body to meet the changing metabolic demands. The recruitment of preload in healthy patients leads to an increase in effective circulating blood volume with a concomitant increase in cardiac output. However, in the setting of heart failure (HF), preload augmentation may precipitate HF decompensation. In this review, we focus on the role of splanchnic nerve modulation and pharmacological therapeutic interventions to prevent HF decompensation through preload reduction. Furthermore, we explore the emerging device-based approaches for cardiac preload reduction while reviewing the ongoing clinical trials.