The design aspects for building a megasonic reactor for separation of food materials from liquid/liquid or solid/liquid mixtures are presented in this review. These aspects are based on the theoretical principles of acoustic particle manipulation such as the acoustic primary and secondary radiation forces, acoustic streaming and the properties of food materials. Key considerations for the design of megasonic reactors are reviewed, which include the transducer selection, positioning and alignment, as well as construction materials and geometry of transducers and reactor. The design of these reactors is discussed around various food applications including palm oil separation, milk fat separation and fractionation, yeast separation in fermentation processes and separation of microalgae.