Basic research of the pathobiology of diseases as well as of therapeutic strategies usually is carried out in rodents as animal models. Translational research that transfers novel results from basic research to clinical application often requires analyses in additional nonrodent models and/or large animal models that share specific pathophysiological characteristics with the human diseases in question. As prerequisites for the generation of appropriate disease models by genetic engineering, pigs exhibit suitable reproductive performance traits, pig genome analyses resulted in the availability of several resources of genomic data, and efficient and precise techniques for the genetic modification of pigs have been established. In the recent years, genetically engineered pigs were increasingly generated as biomedical research tools for specific human genetic diseases. Here, we review the current state of the techniques used for the production of genetically engineered pigs as well as the establishment of genetically engineered pigs as models for human diseases.