Caenorhabditis elegans (C. elegans), a nematode first described in 1900 and later established as a model organism by Sydney Brenner in the 1960s, has become a significant tool for studying neurodegenerative diseases. Its genome was the first to be sequenced among multicellular organisms, providing a wealth of information on its biology. C. elegans is easy to cultivate in the lab with Escherichia coli as its food source and its small size, transparency, and rapid life cycle make it ideal for biological research. The organism progresses through four larval stages before reaching adulthood, with adult hermaphrodites capable of self-fertilization. The nervous system of C. elegans is well-mapped, consisting of 302 neurons in hermaphrodites and 383 in males, the latter having additional neurons for male-specific behaviors. These neurons are primarily simple monopolar or bipolar structures with unbranched processes. C. elegans is used to study various aspects of neurodegeneration, such as morphological changes in neurons, genomic instability, loss of proteostasis, mitochondrial dysfunction, cellular senescence, altered cell communication, and the expression of disease-related proteins. It also allows for the examination of factors affecting lifespan or health span. Research on C. elegans has shed light on conserved neurodegenerative pathways, including the insulin/IGF signaling pathway, the target of rapamycin (TOR) signaling pathway, the AMP-activated protein kinase (AMPK) pathway, and the germline signaling pathway. These pathways are essential for understanding aging and neurodegeneration. Behavioral assays in C. elegans are crucial for assessing the functional outcomes of neurodegenerative models, such as motor deficits, sensory perception, learning, memory, and reproductive behaviors. C. elegans models have been used to study diseases like Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, frontotemporal dementia, and Huntington’s disease. The simplicity of its nervous system, compared to humans, allows for the study of neuronal function and neural circuits in a manageable way, despite the more complex network of connections and cell interactions found in humans. The goal is to translate insights from C. elegans research into a better understanding of the pathology of neurodegenerative diseases.