Ruminants were among the first domesticated animals and have been providing food, leather, wool, draft and by-products to humanity for at least 10,000 years. However, rumen methanogens reduce CO2 to CH4 in association with other rumen microbes that generate substrates for methanogenesis. Consequently, other rumen microbiota can directly and indirectly impact the abundance and activity of methanogens. Enteric methanogenesis from ruminants accounts for approximately 6% of total anthropogenic greenhouse gases emissions and can represent from 2 to12% of the host’s gross energy intake. A myriad of strategies to mitigate CH4 emissions have been investigated, but few have been adopted by industry. This chapter reviews rumen- and feed-associated factors affecting CH4 production and outlines the challenges associated with achieving a reduction in enteric CH4 emissions. The pros and cons of these strategies are discussed in an attempt to define the best approaches to mitigate CH4 emissions from ruminant production systems.