Objective Clinicians often need to evaluate the treatment response of an individual person and to know that observed change is true improvement or worsening beyond usual week-to-week changes. This paper gives clinicians tools to evaluate individual changes on the MATRICS Consensus Cognitive Battery (MCCB). We compare three different approaches: a descriptive analysis of MCCB test–retest performance with no intervention, a reliable change index (RCI) approach controlling for average practice effects, and a regression approach. Method Data were gathered as part of the MATRICS PASS study (Nuechterlein et al., 2008). A total of 159 people with schizophrenia completed the MCCB at baseline and 4weeks later. Data were analyzed using an RCI and a regression formula establishing confidence intervals. Results The RCI and regression approaches agree within one point when baseline values are close to the sample mean. However, the regression approach offers more accurate limits for expected change at the tails of the distribution of baseline scores. Conclusions Although both approaches have their merits, the regression approach provides the most accurate measure of significant change across the full range of scores. As the RCI does not account for regression to the mean and has confidence limits that remain constant across baseline scores, the RCI approach effectively gives narrower confidence limits around an inaccurately predicted average change value. Further, despite the high test–retest reliability of the MCCB, a change in an individual's score must be relatively large to be confident that it is beyond normal month-to-month variation.