Serum-free culture is used routinely for many cell types, especially if transformed, e.g. CHO, hybridoma and recombinant myeloma cell lines. Serum-free medium reduces operating costs and process variability, and removes a potential source of infectious agents. The removal of the components of serum and the elimination of other animal-derived raw materials are proving more challenging. Nevertheless, careful risk/benefit analyses to target R&D toward critical materials is presenting several solutions in this area. A risk/benefit analysis is required for each component replacing serum or serum derivatives. Specific serum proteins used in serum-free media can be eliminated. At present large scale protein-free processes are not routine.