People with multiple sclerosis (MS) often undergo repeated assessments. Methods for determining whether an individual's change in test results over time is reliable require further study. A sample of individuals with MS (N = 52) was assessed at baseline and at 6-month follow-up using the Paced Auditory Serial Addition Test (PASAT), Simple Adjusting–Paced Serial Addition Test (A-PSAT), and Victoria Stroop test. Two methods for determining the reliability of an individual's change over time were examined. The Reliable Change Index (RCI) identified few individuals who declined reliably between baseline and 6-month follow-up. The standard deviation (SD) method of calculation resulted in reliable declines for a small number of individuals on most measures. Use of the SD method resulted in a larger number of individuals who improved reliably. Responsiveness of individuals to treatment effects can be lost in group analyses. The data presented here provide clinicians with an approach for determining whether an individual's change over time on commonly used neuropsychological tests reflects reliable improvement or decline.