During normothermic machine perfusion (NMP), several red flags may prompt declining a liver for transplantation. The most critical biochemical warning is failure to clear lactate to <2–2.5 mmol/L within 2–3 hours, or a rebound rise after initial clearance, indicating poor hepatocellular metabolism. Persistent metabolic acidosis despite heavy bicarbonate support and sharply rising ALT/AST (especially ALT >6000 IU/L) reflect ongoing hepatocellular injury. Perfusion parameters such as low hepatic artery (<150 mL/min) or portal flow (<500 mL/min) at target pressures, or rising vascular resistance, signal microvascular dysfunction. Absent or minimal bile output and, more importantly, abnormal bile chemistry (acidic pH <7.4, high bile glucose nearly equal to perfusate) are strong predictors of biliary complications and graft non-viability. Morphological red flags include patchy discoloration, uneven perfusion, severe steatosis, or firm/nodular architecture. Histology, if available, showing extensive hepatocyte necrosis, endothelial injury, or cholangiocyte death further supports declining. While absolute thresholds vary between centers, the combination of failing metabolic recovery, poor perfusion, absent bile, and histologic injury reliably predicts a high risk of primary non-function or ischemic cholangiopathy, making such livers unsuitable for transplant.