Biotherapeutic protein formulations are often high concentration liquid protein solutions, which are required to be stable under pharmaceutically relevant storage conditions and presence of external stress. Non-ionic detergents like polysorbate have been the most commonly used detergent to maintain formulation stability. Recently, particle formation in polysorbate containing biotherapeutic formulations has arisen as a major quality concern and potential patient risk factor. In this review, we provide a general overview into (i) degradation of polysorbates, (ii) polysorbate analytics, (iii) particle formation induced by polysorbate degradation and root causes thereof, (iv) particle composition and (v) various influencing factors that might lead to particle formation. Consequently, we explore the role of polysorbate degradation in particle formation. Additionally, various degradation pathways and the current discussed root causes are reviewed.