Incurable diseases that are rapidly rising in prevalence, such as Parkinson's disease. There is an urgent need to develop new and more effective therapeutic strategies to combat these devastating diseases. Models – from cell-based systems, to unicellular organisms, to complex animals – have proven to be a useful tool to help the research community shed light on the mechanisms underlying neurodegenerative diseases, and these advances have now begun to provide promising therapeutic avenues. In this themed issue of Disease Models & Mechanisms, a special collection of articles focused on neurodegenerative diseases is introduced. The collection includes original research articles that provide new insights into the complex pathophysiology of such diseases, revealing candidate biomarkers or therapeutic targets. Some of the articles describe a new disease model that enables deeper exploration of key mechanisms. We also present a series of reviews that highlight some of the recent translational advances made in studies of neurodegenerative diseases.