In this review the lyophilization of biotechnology products is discussed. It is emphasized that the final quality of a protein product is determined by an interplay between the proper choice of excipients and the freeze-drying process. A crystalline matrix after freeze-drying is detrimental for the protein product. A glassy amorphous state is a prerequisite for stability, however a glassy state as such will not assure sufficient stability. The glass temperature which defines the state of the freeze-dried cake can be influenced by the moisture content and the choice of excipients.