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Membrane separation processes have become part of the set of basic unit operations for dairy process design and product development. These processes are employed in a variety of separation and concentration duties, but in all cases, the membranes must be cleaned regularly to remove both organic and inorganic material deposited on the surface from the fluid stream being processed. Cleaning is a vital step in maintaining the permeability and selectivity of the membrane and is necessary to return the plant to its original capacity, to minimize risks of bacteriological contamination, and to produce acceptable products. Caustic-, acidic-, and enzyme-based cleaners may be used for membrane cleaning and are usually formulated with additives to best match the specific cleaning duty. Cleaning generates significant volumes of wastewater and reduces membrane life and plant productivity, so each regime must be optimized with respect to concentration, order and duration of cleaning steps, temperature, pressure, and flow rate. This article reviews the key mechanisms governing cleaning performance and suggests directions by which further optimization may be achieved.