Upon the approval of disease-modifying therapies (DMTs) for patients with active secondary progressive phase of multiple sclerosis (SPMS), there became an emerging need to prospectively predict and diagnose patients transitioning from the relapsing-remitting to the secondary progressive phase of MS. Whilst several research articles handle the challenges for diagnosing this stage of the disease, a clear step-by-step diagnostic approach remains elusive. This review aims at providing a step-by-step diagnostic approach to patients within 'transitioning' MS based on the currently available research findings and to summarize the gaps in the diagnostic approach and the recommendations for future research in this area of practice.