The adverse prognostic implications of significant renal dysfunction during treatment of acute decompensated heart failure (HF) in patients with obese HF and preserved ejection fraction (HFpEF) provide strong rationale for development of therapeutic strategies that enhance decongestion while preserving renal function in this cohort. The combination of preload sensitivity, intrinsic renal dysfunction related to obesity, glomerular hyperfiltration, reversible renal hypoperfusion (poor renal arterial perfusion and renal venous congestion), and decreased systemic vascular resistance in obesity may predispose patients to renal hemodynamic compromise during diuresis. Thus, serum creatinine increase should not be evaluated in isolation but rather considered in the context of the entire clinical picture in patients with obese HFpEF.