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The isoelectric behavior of food proteins has been well characterized in the food science literature. The isoelectric point (pI) of a protein is a pH at which the protein maintains a zero net electrostatic charge. In this state, protein-protein hydrophobic interactions overcome protein-water electrostatic interactions and the minimum solubility of proteins results. Consequently, several food science laboratories have begun active research on the application of the pI to recover functional muscle proteins, particularly fish myofibrillar proteins. Fish stocks are declining and several fisheries are currently over-exploited and may collapse by mid century. Fish processing by-products are considerable and include heads, frames, viscera, and etc. By-products are land-filled, ground-and-discarded or otherwise diverted from human consumption. By-products retain ample muscle proteins and oil. The oil contains omega-3 fatty acids. Due to the lack of commercially available technology to recover proteins and lipids from fish processing by-products or underutilized aquatic species, this tremendous resource is currently unavailable for human consumption. Fish proteins and oil from otherwise low-value by-products can be recovered using isoelectric solubilization/precipitation with recovery yields of approximately 90%. Recovered proteins and oil retain functionality and nutritional value for human food products. This article reviews the fundamental biochemical principles of food proteins and lipids as well as their structure and interaction with water in relation to the isoelectric behavior. Additionally, the most recent developments regarding application of isoelectric solubilization/precipitation to recover functional and nutritious proteins and oil from fish processing byproducts and underutilized aquatic species are addressed.