Background. A number of studies have computed the minimally important difference (MID) for health-related quality of life instruments. Objective. To determine whether there is consistency in the magnitude of MID estimates from different instruments. Methods. We conducted a systematic review of the literature to identify studies that computed an MID and contained sufficient information to compute an effect size (ES). Thirty-eight studies fulfilled the criteria, resulting in 62 ESs. Results. For all but 6 studies, the MID estimates were close to one half a SD (mean = 0.495, SD = 0.155). There was no consistent relationship with factors such as disease-specific or generic instrument or the number of response options. Negative changes were not associated with larger ESs. Population-based estimation procedures and brief follow-up were associated with smaller ESs, and acute conditions with larger ESs. An explanation for this consistency is that research in psychology has shown that the limit of people’s ability to discriminate over a wide range of tasks is approximately 1 part in 7, which is very close to half a SD. Conclusion. In most circumstances, the threshold of discrimination for changes in health-related quality of life for chronic diseases appears to be approximately half a SD. The interpretation of changes in health-related quality of life (HRQL) has been a research focus for more than a decade. 1 More recently, researchers have been devising methods to identify a minimal level of change consistent with real, as opposed to statistically significant, benefit. 2 The determination of the minimal level of real change for any HRQL scale can be a daunting task. It may potentially vary for different questionnaires, different diseases, and different demographic groups. Potential influences related to the questionnaire itself include the relative position of the individual on the HRQL scale (ie, floor and ceiling effects 3), the number of steps on the scale, the number of items, and so forth. The intent of the analysis (making a diagnosis vs. testing the efficacy of an intervention) and the identity of the individual performing the assessment (patient vs. clinical staff) could potentially result in a different estimate of important change. Collectively, considering all these variables for each measure, this variation represents a prohibitive impediment to the successful implementation of HRQL endpoints in clinical research and practice. However, there is some evidence that some of these various factors may have a relatively small impact on the magnitude of the minimal difference. Certainly, some authors have noted that, over a series of studies with a diversity of conditions and age groups using disease-specific measures with 7-point response scales, the minimally important difference (MID) appears to fall consistently close to 0.5 points on the 7-point scale. 1,4,5 It is the thesis of the present article that there is more commonality than difference in the variety of approaches. We will show that a multiplicity of methods, using several different scales from time tradeoff to visual analogue, with the number of items ranging from 1 to more than 50, in a diversity of chronic conditions, led to remarkably similar estimates. We will argue that this convergence is not accidental, but is a direct consequence of the limit of human discrimination ability. Finally, we will point out some circumstances that diverge from this consistency.