Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. The etiology of MS involves a complex interplay of genetic predisposition and environmental risk factors, including Epstein–Barr virus infection or vitamin D deficiency. This chapter provides a comprehensive overview of MS epidemiology, clinical presentation, diagnostic criteria, and paraclinical investigations. A wide spectrum of neurological symptoms and signs is discussed, highlighting the importance of distinguishing typical from atypical features and identifying red flags that may suggest alternative diagnoses. The current 2017 McDonald criteria, alongside proposed 2024 revisions, are summarized with emphasis on their diagnostic principles, limitations, and potential updates including central vein sign, paramagnetic rim lesions, and kappa free light chains. Magnetic resonance imaging (MRI) remains a cornerstone of diagnosis, with detailed descriptions of MS-typical brain and spinal cord lesions, their distribution, morphology, and temporal evolution. Important imaging red flags and mimickers are outlined. The chapter further reviews cerebrospinal fluid findings (CSF), including oligoclonal bands (OCB) and emerging biomarkers such as the kappa free light chain (KFLC) index, as well as ophthalmologic and neurophysiological assessments that aid in diagnostic confirmation. Disease-modifying treatments, relapse management strategies, and the role of early intervention are also discussed, underlining the prognostic benefits of prompt initiation of therapy. This chapter serves as a foundational reference for understanding the clinical and paraclinical features of MS and offers guidance on recognizing atypical presentations that may warrant further investigation.