Purpose of Review <p>Multiple Sclerosis (MS) is a chronic inflammatory neurological disorder affecting over 2.8 million people worldwide. It is characterized by distinct phenotypes, such as relapsing-remitting MS (RRMS) and progressive forms (SPMS, PPMS). While disease-modifying therapies (DMTs) effectively target inflammation and reduce relapse rates in RRMS, they are less effective in progressive MS, where neurodegeneration becomes more prominent. This review explores the emerging role of the microtubule-associated protein tau, typically associated with neurodegenerative diseases like Alzheimer’s disease, in MS pathology and its potential as a therapeutic target.</p> Recent Findings <p>Tau is primarily involved in stabilizing neuronal microtubules. Under pathological conditions, tau alters and aggregates into neurofibrillary tangles, contributing to neuronal dysfunction and degeneration. Recent studies have identified tau seeds and pathological tau in MS, particularly in and adjacent to lesions in human brain tissue and rodent models of MS. Evidence suggests a bidirectional relationship between tau pathology and inflammation, where tau drives inflammatory responses, and inflammation exacerbates tau aggregation. However, understanding the role of tau in MS remains limited, particularly in progressive forms where neurodegeneration is most severe.</p> Summary <p>The involvement of tau in MS represents a promising avenue for research and therapeutic intervention, particularly in progressive forms of the disease. Addressing gaps in knowledge, such as developing better MS models, investigating tau aggregation in MS, and identifying reliable biomarkers, could pave the way for novel tau-targeted therapies. Such approaches hold the potential to mitigate neurodegeneration and improve outcomes for patients with progressive MS.</p>