Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis (ALS), represent a major global health challenge. Characterized by progressive loss of neurons and neurological function, these disorders lead to cognitive decline, motor dysfunction, and ultimately severe disability. Despite significant research, effective therapies remain limited, primarily due to the complex etiology and heterogeneous nature of neurodegeneration. Biomedical research has focused on developing experimental models to understand the molecular mechanisms underlying neurodegenerative diseases and to evaluate potential therapeutic strategies. Disease models, ranging from in vitro cellular systems to in vivo animal models, have provided critical insights into pathological pathways such as protein misfolding, oxidative stress, mitochondrial dysfunction, and neuroinflammation. This article explores the current neurodegenerative disease models, their contributions to biomedical research, advantages, limitations, and future perspectives.