Ionophores (such as monensin, lasalocid, laidlomycin, salinomycin and narasin) are antimicrobial compounds that are commonly fed to ruminant animals to improve feed efficiency. These antimicrobials specifically target the ruminal bacterial population and alter the microbial ecology of the intestinal microbial consortium, resulting in increased carbon and nitrogen retention by the animal, increasing production efficiency. Ionophores transport ions across cell membranes of susceptible bacteria, dissipating ion gradients and uncoupling energy expenditures from growth, killing these bacteria. Not all bacteria are susceptible to ionophores, and several species have been shown to develop several mechanisms of ionophore resistance. The prophylactic use of antimicrobials as growth promotants in food animals has fallen under greater scrutiny due to fears of the spread of antibiotic resistance. Because of the complexity and high degree of specificity of ionophore resistance, it appears that ionophores do not contribute to the development of antibiotic resistance to important human drugs. Therefore it appears that ionophores will continue to play a significant role in improving the efficiency of animal production in the future.