Certain demographic characteristics and cerebrospinal fluid (CSF) or serum biomarkers can serve as critical red flags when evaluating a suspected diagnosis of multiple sclerosis (MS). This chapter provides a structured overview of common mimickers of pediatric-onset MS (POMS) and late-onset MS (LOMS). While MS typically presents between the ages of 20 and 40 years, an atypical age of onset significantly increases the likelihood of alternative diagnoses, such as neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), inherited metabolic disorders, paraneoplastic syndromes, vascular conditions, and infectious or systemic inflammatory diseases. The chapter further discusses CSF abnormalities that may challenge the diagnosis of MS, including elevated lactate concentrations—more typical for mitochondrial diseases, infections, or tumors—and the significant presence of eosinophils or neutrophils, which are highly unusual in MS but may signal NMOSD, sarcoidosis, or parasitic infections. In addition, the diagnostic value and limitations of CSF-restricted oligoclonal bands (OCB) are critically appraised. Although OCB are highly sensitive for MS in Western populations, their absence or disappearance over time, or their transient presence during attacks in other conditions such as acute disseminated encephalomyelitis (ADEM), MOGAD, or systemic lupus erythematosus (SLE), should prompt consideration of alternative diagnoses. Through illustrative examples and summary tables, this chapter provides clinicians with practical guidance to recognize key demographic and biochemical red flags that may indicate a non-MS etiology in patients with demyelinating syndromes.