Mass Spectrometry has commonly been used in the semi-conductor industry where maintaining a clean environment with minimum contaminants under high vacuum is crucial for successful manufacturing. Since the technology’s early usage for pharmaceutical manufacturing in the 1980 s, particularly in the freeze-drying environment, much has changed. The focus of the current work is aimed at asking some key questions regarding the maturity of the technology, its challenges and importance of having an application-specific instrument for quantitative process analyses applied to freeze-drying. Furthermore, we compare the use of mass spectrometers in early installations from the ’80s with recent experiences of the technology in the production and laboratory environments comparing data from different MS technologies. In addition, the manuscript covers broad application of the technology towards detection of and sensitivity for analytes including silicone oil and Helium. It also explores the option of using MS in detecting water vapor and nitrogen concentration not just in primary drying, but also in secondary drying. The technology, when purpose built, has the potential for use as a robust, multi-purpose PAT tool in the freeze-drying laboratory and production environments.