Infections due to antibiotic-resistant organisms are increasing in prevalence and represent a major public health threat. Antibiotic overuse is a major driver of this epidemic, and antibiotic stewardship an important means of limiting antibiotic resistance. The intensive care unit (ICU) setting presents an intersection of opportunities and challenges for effective antibiotic stewardship, but limited data inform optimal stewardship interventions in this setting. In this review, we present unique considerations for stewardship interventions the ICU setting and summarize available data evaluating the impact of prospective audit and feedback, diagnostic test stewardship, rapid molecular diagnostic tests, and procalcitonin-guided algorithms for antibiotic discontinuation. The existing knowledge gaps ripe for future research are emphasized.