Methane emissions from ruminants are widely recognized as one of the major factors contributing to global climate change. Methane stemming from the fermentation process in the rumen is produced by methanogenic archaea, which make up only a small proportion of the total microbial community (1-4%). One strategy for mitigating these emissions is to develop compounds that specifically inhibit rumen methanogens. To accelerate inhibitor discovery, X-ray crystallographic techniques were used to determine the structures of enzymes involved in specialized biochemical pathways of rumen methanogens, including methanogenesis, cofactor biosynthesis and archaeal lipid synthesis. Over three hundred enzymes were targeted for structure determination, producing in excess of one hundred soluble enzymes for crystallographic screening. Over thirty different enzymes have produced crystals and thirteen structures have been solved thus far, five of which have been the focus of in silico screening to identify possible inhibitors for use in ruminants.