In the microbiology laboratory, sterility is a most important consideration and ways of achieving it form the earliest portions of the training of a microbiologist. In the fermentation industry, contamination by unwanted organisms could pose serious problems because of the vastly increased scale operation in comparison with laboratory work. If Pediococcus (Streptococcus) damnosus which causes sourness in beer were to contaminate the fermentation tanks of a brewery, hundreds of thousands of liters of beer may have to be discarded resulting in loss of revenue. The situation would be similar if a penicillianase-producing Bacillus species were to contaminate a penicillin fermentation, or lytic phages contaminate an acetone-butanol mash. The contaminant may utilize the components of the fermentation broth to produce unwanted end-products and therefore reduce yield or produce by-products not removable in the established extraction process. Although contaminants are generally undesirable, not all fermentation need to be carried out under strict asepsis such as in bulk products as yeasts or industrial alcohol. This chapter discusses the basis of loss due to microbial contaminants, physical methods and chemical methods of achieving sterility, aspects of sterilization in industry, the sterilization of the fermenter and its accessories, media sterilization, and phage contamination.