Understanding of both host physiological and microbial associated factors that influence feed utilization efficiency is instrumental in enhancing cattle's production efficiency and lowering the environmental impact of cattle production. Due to its high microbial diversity and density as well as the large epithelial surface, the rumen plays a key role not only in digestion but also in modulatory functions of the host's immune responses, and overall health. In addition, rumen epithelium is a very intensive metabolic tissue, and its metabolic efficiency is also crucial for the digestive efficiency. Short chain fatty acids (SCFA) and methane, generated in the rumen as end-products of fermentation, are closely though differently related to cattle's efficiency in feed utilization and production. While efforts are made to lower methane emissions as an instrument to improve cattle's efficiency, it has become of great interest to enhance production, absorption and metabolism of SCFA across multilayer rumen epithelia, because this event enhances the output of energy to the host. Also, the efficient absorption of SCFA across rumen epithelia is involved in the regulation of luminal pH and prevention of rumen acidosis, which in many cases is associated with ruminal ecosystem disturbances and systemic disorders. Although diet has a profound effect on SCFA production, methanogenesis, and rumen health, cattle do respond differently to nutritional challenges. This animal variation appears to be associated with differences in rumen microbial communities as well as rumen SCFA absorption and metabolism. The latter greatly depends on morphological adaptations and the metabolic capacity of the lining epithelium of the rumen wall. Furthermore, various host's abilities in mounting an immunological response might also be involved in the divergence of cattle's feed efficiency due to changes in energy and nutrient partitioning. Thorough understanding of rumen microbial ecology and metabolism, rumen epithelia physiology as well as their interactions with the host could lead to sustainable strategies for improving feed efficiency in cattle. The present review article summarizes the most recent findings and emphasizes the crucial role of rumen-related factors that may have consequences for variation in feed efficiency of cattle. (C) 2014 Elsevier B.V. All rights reserved.