Use of plant polyphenols in production animal agriculture is increasingly being investigated, especially in the face of heavier restrictions on antibiotic use. Flavonoids are a class of polyphenols known to have anti-inflammatory and anti-oxidative functions. The aim of this review is to discuss the use of flavonoids in the areas of neonatal health, animal growth, efficiency of rumen fermentation, milk production, and resilience to stress in dairy cows. Bioavailability of flavonoids is typically greater in the aglycone form in humans and monogastric species; however, in ruminants the aglycone can be quickly degraded by rumen microbes. Bioavailability studies have demonstrated that although the aglycone form is the more bioavailable source in neonatal calves, as the rumen develops, the glycosylation of flavonoids provides a degree of ruminal protection and therefore improves bioavailability. Flavonoid supplementation appears to be most beneficial during periods of stress. In growing ruminants, flavonoid supplementation had little impact on metabolism, health status, or growth parameters, but did reduce the severity of pathogenic and nonpathogenic diarrhea. Flavonoids lessened the drop in ruminal pH and reduced the inflammatory state of cows fed a high grain diet and during induced subacute ruminal acidosis. Several studies supplementing different flavonoids to dairy cows during the transition period showed their potential to reduce postpartum inflammation, endoplasmic reticular stress, and hepatic lipid accumulation. In addition, milk yield was increased in most studies over the transition to lactation, but milk component responses were varied. Milk somatic cell concentration was often reduced by dietary flavonoids, and they have been effective at suppressing inflammation and apoptosis in pathogen-induced mouse mastitis models. Further research is warranted to investigate the potential of flavonoids to reduce mastitis in dairy cows. Overall, flavonoids can increase ruminant productivity with beneficial effects exhibited under a variety of stressful conditions; however, unexplained variability in response to flavonoid supplementation is likely due to differences in dose, specific compound efficacy, and mode of action.