The rumen is an integrated dynamic microbial ecosystem composed of enormous populations of bacteria, protozoa, fungi, archaea, and bacteriophages. These microbes ferment feed organic matter consumed by ruminants to produce beneficial products such as microbial biomass and short-chain fatty acids, which form the major metabolic fuels for ruminants. The fermentation process also involves inefficient end product formation for both host animals and the environment, such as ammonia, methane, and carbon dioxide production. In typical conditions of ruminal fermentation, microbiota does not produce an optimal mixture of enzymes to maximize plant cell wall degradation or synthesize maximum microbial protein. Well-functioning rumen can be achieved through microbial manipulation by alteration of rumen microbiome composition to enhance specific beneficial fermentation pathways while minimizing or altering inefficient fermentation pathways. Therefore, manipulating ruminal fermentation is useful to improve feed conversion efficiency, animal productivity, and product quality. Understanding rumen microbial diversity and dynamics is crucial to maximize animal production efficiency and mitigate the emission of greenhouse gases from ruminants. This chapter discusses genetic and nongenetic rumen manipulation methods to achieve better rumen microbial fermentation including improvement of fibrolytic activity, inhibition of methanogenesis, prevention of acidosis, and balancing rumen ammonia concentration for optimal microbial protein synthesis.