Medical practice is increasingly informed by the evidence from randomized controlled trials. When such evidence is not available, clinical hypotheses based on pathophysiological reasoning and common sense guide clinical decision making. One commonly utilized general clinical hypothesis is the assumption that normalizing abnormal laboratory values and physiological parameters will lead to improved patient outcomes. We refer to the general use of this clinical hypothesis to guide medical therapeutics as the "normalization heuristic". In this paper, we operationally define this heuristic and discuss its limitations as a rule of thumb for clinical decision making. We review historical and contemporaneous examples of normalization practices as empirical evidence for the normalization heuristic and to highlight its frailty as a guide for clinical decision making.