Accumulating neurological disability has a substantial impact on the lives of patients with multiple sclerosis (MS). As well as the established Expanded Disability Status Scale (EDSS), several other outcome measures are now available for assessing disability progression in MS. This review extends the findings of a previous analysis of relapsing-remitting MS (RRMS) trials published up to 2012, to determine whether there has been a shift in outcome measures used to assess disability in phase III clinical trials in RRMS and progressive MS. Forty relevant trials were identified (RRMS, n = 16; progressive MS, n = 18; other/mixed phenotypes, n = 6). Sustained EDSS worsening, particularly over 3 months, was included as an endpoint in almost all identified trials. Other disability-related endpoints included the Multiple Sclerosis Functional Composite z-score and scores for the physical component summary of the Multiple Sclerosis Impact Scale and Medical Outcomes Study Short-Form (36-item) Health Survey. Tests assessing manual dexterity, ambulation, vision and cognition were also employed, and in some trials, composite endpoints were used. However, there was no obvious trend in choice of disability outcome measures over time. Sustained EDSS worsening over short time periods continues to be the most widely used measure of disability progression in pivotal MS trials, despite its well-recognised limitations. A new tool set is needed for use in MS clinical trials that detects the benefit of potential treatments that slow (or reverse) progressive disability.