This paper describes in a historical perspective the development of serum-free nutrient media suitable for long-term culturing of nerve tissue. Several disadvantages of the use of serum are discussed, coupled with an acknowledgement that it is not always advisable to replace a routinely used serum-supplemented medium by a chemically defined medium with the expectation of immediate success. Therefore a strategy is given on how to develop a chemically defined medium that is thoroughly tuned to the specific needs of the cell type to be cultured. It is argued that such a medium has several substantial advantages over the use of serum.