This editorial summarizes the key observations from a special issue of Animal Health Research Reviews comprising 14 articles related to the efficacy of antimicrobial and non-antimicrobial approaches to reduce disease in beef, dairy cattle, swine, and broiler chickens. The articles used evidence-based methods, including scoping reviews, systematic reviews, meta-analyses, and network meta-analyses. Despite finding evidence of efficacy for some of the interventions examined, across the body of research, there was a lack of replication and inconsistency in outcomes among the included trials, and concerns related to completeness of reporting and trial design and execution. There is an urgent need for more and better data to inform antimicrobial stewardship practices in animal agriculture.