People with multiple sclerosis (pwMS) often experience disability progression even when receiving disease-modifying therapies that effectively suppress relapses. This phenomenon is commonly referred to as progression independent of relapse activity (PIRA). Currently, it is challenging to characterize pwMS who are experiencing disability progression in clinical practice. Existing definitions of PIRA rely primarily on the Expanded Disability Status Scale (EDSS), which is biased towards ambulation and does not effectively capture the gradual accumulation of symptoms and signs across other clinical areas associated with disability progression. Here, we propose a step-by-step approach that neurologists can use in clinical practice to identify pwMS experiencing disability progression irrespective of age, EDSS, or disease duration. By using this approach, neurologists can assess the presence or absence of specific variables to help determine if disability is stable or progressing. This could enable appropriate treatments to be implemented in a timely manner, particularly as new disability-targeting therapies become available.