The 99th percentile of cardiac troponin assays for determining the presence of acute myocardial infarction (AMI) was set when assay analytical performance was much less precise than currently and was chosen, in part, to reduce the frequency of 'false-positive' results. A result greater than 99th percentile criterion has been a requirement of each version of the universal definition of MI. It also became used as a dichotomous decision-making threshold in diagnostic strategies for investigating AMI in acute care settings. There are numerous difficulties in deriving the 99th percentile which undermine its reliability as a standalone test threshold. It is important for patient safety that all users are aware of the challenges and pitfalls of using the 99th percentile for decision-making. We present a focused review of the 99th percentile, highlighting some difficulties with its use as a decision threshold as well as possible adjunctive strategies and alternative approaches.