Transglutaminases can perform various reactions that are based on cross-linking, acyl-transfer and deamidation. These enzymes are found in many different organisms where they have very specific roles. The basic reaction mechanism of these transglutaminases is similar. The reactions catalyzed by transglutaminases have proven to be useful in production of different kinds of protein ingredients and food products. In this review, we will show important aspects of transglutaminase cross-linking in respect to substrate specificity, accessibility of proteins, regulation and differences in reactions and safety. These aspects will be viewed in respect to food applications.