The presence of ubiquitinated protein inclusions is a hallmark of most adult onset neurodegenerative disorders. Results from several neurodegenerative model systems indicate that elimination of the disease-associated inclusions can lead to symptomatic reversal, and a better understanding of the mechanisms involved in accumulation and turnover of aggregation-prone proteins is therefore important. Autophagy has been found to contribute to protein aggregate clearance, and the term aggrephagy is used to describe the selective degradation of aggregation-prone proteins by autophagy. Here, we provide an overview of different disease-related model systems and assays that can be used to distinguish non-aggregated from aggregation-prone proteins, and how these assays can be used to determine turnover of protein aggregates by autophagy.