Proteinopathies are diseases in which specific proteins misfold, aggregate, and accumulate within cells or tissues, leading to cellular dysfunction and degeneration. Proteinopathies are mostly age-related and often associated with neurodegenerative disorders like Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In these diseases, proteins such as Amyloid beta (Aβ), Tau, α-synuclein, TDP-43, and polyglutamine-expanded proteins misfold and aggregate, disrupting many cellular processes, ultimately leading to cell death. These pathological aggregates typically form due to a failure of protein quality control (PQC) mechanisms that maintain cellular proteostasis. Age-related decline in PQC systems exacerbates the accumulation of toxic protein aggregates, contributing to disease progression. This chapter highlights the use of the model system Caenorhabditis elegans to investigate the molecular basis of proteinopathies. We focus on transgenic C. elegans models expressing human disease-related proteins, which recapitulate key features of protein aggregation and toxicity. We also provide information on the availability of these strains.