Advances in the understanding of multiple sclerosis and the development of biomarkers of pathophysiology prompted a substantial revision of the 2017 McDonald diagnostic criteria. The new 2024 McDonald criteria provide a unified approach for diagnosing multiple sclerosis in individuals with relapsing or progressive courses throughout the lifespan (ie, from paediatric to late-life presentations). The optic nerve can now serve as a fifth anatomical location within the CNS for diagnosis. The central vein sign, paramagnetic rim lesions, and kappa free-light chain concentrations in CSF can be used, when available, to provide supportive evidence and confer specificity for a diagnosis of multiple sclerosis in specific situations. In certain cases, radiologically isolated syndrome or neurological symptoms that do not constitute a clear attack or progression of disability can fulfil the criteria for a multiple sclerosis diagnosis. We also provide guidance for the diagnosis of multiple sclerosis in older individuals (≥50 years) and those with comorbidities. The 2024 revised criteria should expedite the diagnosis of multiple sclerosis, while maintaining specificity.