Diuretic volume reduction continues to be the mainstay of congestive heart failure (CHF) management globally. However, diuretic resistance is a critical topic that lacks standardized evidence-based management guidelines accounting for mechanisms of diuretic resistance, renal function, and co-morbidities. Major healthcare utilization consequences result from this. The authors herein reconcile the definition of renal functional decline with emphasis on biomarker-driven assessment. Novel goal-directed treatment approaches are reviewed including hypertonic saline, acetazolamide, sodium-glucose transporter inhibition, sequential nephron blockade and Elabela-APJ axis targeting are reviewed, as well as percutaneous visceral splanchnic sympathectomy (converting a volume-focused to a distribution-focused paradigm).