Yeast models of neurodegenerative diseases associated with protein misfolding and protein aggregation have given unique insights into the underlying genetic and cellular pathomechanisms. These yeast models recapitulate central aspects of protein misfolding and the ensuing toxicity, such as interference with cellular protein quality control, concentration-dependent formation of insoluble, often amyloid-like aggregates and the associated toxicity. Advanced age is undoubtedly the highest and most common risk factor for most neurodegenerative diseases. Since yeast has served as a superb model to study cellular aspects of aging, we outline strategies to study how aging modulates protein misfolding and its toxicity, thereby opening new avenues to continue the success of yeast as powerful models to study neurodegenerative diseases.