Ionophores have been widely used in the beef and dairy industry for decades to improve feed efficiency and performance by altering ruminal fermentation dynamics, increasing the level of propionate. Ionophores can also reduce ruminal proteolysis and ammonia synthesis, thus increasing the influx of protein into the small intestine in cattle, leading to improvements in performance and efficiency responses. Ionophores indirectly impact ruminal methanogenesis by decreasing the substrate used to produce methane. Despite the consistent benefits of using ionophores in cattle nutrition, their utilization is under public scrutiny due to concerns related to microbial adaptation. However, there is inconsistent evidence supporting these concerns, whereas ionophores are still an important dietary tool to enhance productivity and profitability in beef production systems.