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Non-native aggregation is a common concern during therapeutic protein product development and manufacturing, particularly for liquid dosage forms. Because aggregates are often net irreversible under the conditions that they form, controlling aggregate levels requires control of aggregation rates across a range of solution conditions. Rational design of product formulation(s) would therefore benefit greatly from methods to accurately predict aggregation rates. This article focuses on the principles underlying current rate-prediction approaches for non-native aggregation, the limitations and strengths of different approaches, and illustrative examples from the authors’ laboratories. The analysis highlights a number of reasons why accurate prediction of aggregation rates remains an outstanding challenge, and suggests some of the important areas for research to ultimately enable improved predictive capabilities in the future.