Multidrug resistant bacterial strains are a current challenge to modern medicine, and according to the Centers for Disease Control and Prevention are responsible for $20 billion in excess healthcare costs, $35 billion in societal costs, and 8 million additional hospital days in the United States. As occurs for clinical use, the administration of antimicrobial drugs in cattle creates selective pressure shown to result, in many cases, in resistance to antimicrobial drugs critically important to human medicine. Furthermore, the use of antimicrobial drugs in food animals, specifically drugs in classes that are also used in human medicine, remains a contentious public health issue. Studies that identify risk factors that increase the rate of selection, amplification and spread of resistance on dairy farms, and generate information to propose intervention to prevent or reduce such undesired outcomes are of vital importance. The studies in this dissertation focused on this knowledge gap and used epidemiology, microbiology and genomic approaches to generated novel data in many priority areas, including (1) prevalence and concentration of drug residues present in the milk commonly fed to dairy calves; (2) impacts of feeding milk with drug residues on selection of resistant bacteria and on the composition of the fecal microbiota of preweaned calves; (3) effect of preweaned dairy calf housing systems on prevalence of antimicrobial resistance; (4) prevalence of resistant E. coli and Salmonella in cattle under different heifer-raising practices; and (5) efficacy of using ultraviolet light as an intervention to reduce pathogens in the milk and colostrum fed to calves. This dissertation supports the view that intended or unintended exposure of cattle to therapeutic and sub-therapeutic concentrations of antimicrobial drugs can select for resistance to antimicrobials of critical importance to veterinary and human medicine. Moreover it encourages the implementation of management practices that improve the health of cattle without the use of antimicrobials, and endorses the judicious use of antimicrobial drugs concomitant with improvement of animal production and wellbeing.