The therapeutic use of proteins has created an increasing demand for feasible and economical methods for both up- and downstream processes. However, whereas upstream processes have attracted substantial investment and commercial attention, downstream processing has been overlooked, causing a production bottleneck that is shifting the costs of production. This review focuses on the use of aqueous two-phase extraction as an option for the downstream processing of therapeutic proteins. It is a potential and promising liquid-liquid extraction technique for the purification of biomolecules, such as monoclonal antibodies, growth factors and hormones, that combines a high selectivity and biocompatibility with an easy scale-up and continuous operation mode.