The global problem of antibiotic resistance of circulating pathogenic microorganisms was stated by the World Health Organization in 2014. The spread of pathogens with multiple and/or extensive drug resistance is facilitated by the widespread and unsystematic use of antibacterial pharmaceuticals in animal husbandry, including for metaprophylactic purposes and to stimulate productivity. The polyresistance of etiopathogenetic strains of bacteria poses a real threat to public health and the effectiveness of medical care. Based on our own screening studies and a broad current scientific review, system analysis, this paper presents the results of studies on antibiotic resistance and substitution programs in animal husbandry, designed to reduce or eliminate the use of antibiotics for non-therapeutic purposes. The development of the problem of feed antibiotics is revealed, new directions of decontamination and metaprophylaxis in animal husbandry, alternative to the use of antibiotics, are presented. In particular, it has been shown that the use of bacteriophages is of promising importance in solving the problem of bacterial resistance to antibiotics. Antimicrobial peptides, immunoglobulins, organic acids, metal nanoparticles, as well as drugs aimed at stimulating the growth and metabolism of beneficial gastrointestinal bacteria: probiotics, prebiotics, synbiotics and aimed at improving the use of nutrients by the host: food enzymes are given as promising substitutes for phytogenics.