A variety of non-inflammatory neurological disorders, systemic conditions, and even normal variants can mimic inflammatory demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). This chapter provides an in-depth overview of these diverse mimics, including amyotrophic lateral sclerosis (ALS), Bell’s palsy, chemoradiation-induced demyelination, fibromyalgia, functional neurological disorders (FND), headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL), spondylotic and structural myelopathies, traumatic axonal injury (TAI), and normal age-related imaging or cerebrospinal fluid (CSF) findings. Each section reviews the epidemiology, pathophysiology, clinical presentation, neuroimaging patterns, laboratory results, and differential diagnostic challenges. Particular emphasis is placed on distinguishing features such as symptom onset (acute vs. progressive), the presence or absence of sensory involvement, CSF-restricted oligoclonal bands, magnetic resonance imaging (MRI) lesion morphology, and red flags that signal alternative diagnoses. Functional symptoms can be particularly challenging due to overlap with MS and often coexist with it. Meanwhile, fibromyalgia and neuropsychiatric comorbidities are more prevalent in MS and may confound interpretation of vague or non-specific symptoms. Additionally, some post-radiation changes and structural spinal cord pathologies may resemble MS on imaging. Recognizing these mimics is critical to prevent misdiagnosis, avoid unnecessary immunotherapy, and provide appropriate treatment. This chapter concludes with a summary of normal MRI and CSF findings in the general population that can lead to overdiagnosis of MS, especially in the setting of non-specific symptoms. The chapter aims to provide clinicians with practical tools and red flags for distinguishing MS from its mimics across a wide diagnostic spectrum.