Fed-batch cell culture processes are the standard platform technology for the synthesis of high value biopharmaceutical proteins. Recent advances in cell line development and in the optimization of culture medium have enabled the operation of fed-batch processes at significantly higher volumetric productivities than previously realized. While a robust basal medium is essential to ensure high productivity, a well-developed feed medium coupled with an appropriate feeding strategy are essential for sustaining it over the course of the culture duration. Furthermore, optimization of cell culture medium needs to be cognizant of specific goals for its use. Different optimization strategies are adapted for developing platform media applicable for multiple cell lines and customized media developed for specific cell lines. While volumetric productivity continues to be an important parameter for cell culture medium optimization, the developed medium should also be robust during implementation in biopharmaceutical manufacturing facilities. The developed medium should be easy to prepare and have a long shelf life to ensure ease of process implementation in multiple commercial and clinical-scale manufacturing sites. Due care should be taken to ensure that optimization of media does not lead to unacceptable alterations in the quality of the expressed protein. This article will address all these aspects that ensure the efficient optimization and implementation of animal cell culture media.