Whey-based nutritional beverages are often fortified with calcium (Ca) in order to deliver the recommended intake of Ca. However, technical and product quality challenges are often experienced with Ca fortification of whey protein-based nutritional solutions, such as poor heat stability, high viscosity, colloidal instability, and impaired heat transfer. Understanding of the relationships and interactions between whey proteins and Ca relative to liquid process (e.g., ready to feed products, feed material prior to drying) is essential to designing and formulating nutritional whey-based products with desired physicochemical and colloidal stability properties. This article reviews the interactions between whey proteins and Ca salts used in the formulation of nutritional whey-based products as well as major processing implications associated with Ca fortification of whey-based solutions.