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Regression to the mean (RTM) refers to the tendency for a group of cases that differ from the population mean to move (regress) towards the mean, on average, when re-assessed, if scores at the two points are less than perfectly correlated. This paper considers factors that affect the magnitude of RTM and how RTM may impact findings from primary studies and reviews of substance use disorder (SUD) treatment.The paper is guided largely by A Primer on Regression Artifacts by Campbell and Kenny. It reviews potential RTM effects in three areas of SUD treatment research. One is the extent to which within-group improvement in comparative treatment trials, including ‘placebo effects’, is a function of RTM. The second is the vulnerability of treatment evaluations employing non-equivalent control group designs to RTM and biased estimates of treatment effects when matching, or statistical equating is used to adjust for pre-existing group differences. The final issue is the impact of RTM in syntheses of research findings on SUD treatments. In particular, the tendency for later studies of a particular intervention to have smaller treatment effect sizes relative to earlier studies is considered as an RTM phenomenon.RTM is a pervasive, but often unrecognized phenomenon that can bias findings in SUD treatment studies and in systematic reviews of that research.SUD treatment researchers should be aware of RTM, take any available steps to reduce it, and try to diagnose whether it is still affecting research findings.