Antibiotics have long been of great benefit for people, both in the medical treatment of human disease and in animal food where they improve the growth performance and feed utilization during animal production. Antibiotics as in-feed supplements affect all stages of pork production, including the gestation, nursing, growing, and finishing stages, although the effects show stage-dependent differences. However, the use of antibiotics in animal feed has become a worldwide concern. This review describes why sub-therapeutic levels of antibiotic additives in animal feed have become an integral part of animal feeding programs for more than 70 years, particularly in pork production. It also discusses the threat of the long-term use of sub-therapeutic levels of antibiotics in pork production. In recent years, the effectiveness of in-feed antibiotics has tended to decrease. This review analyzes this change from various perspectives. First, the equipment used at pig farms has improved dramatically and is more sanitary. Worldwide, more pig farms use pig farrowing crates, gestation crates, piglet nursery crates, flooring devices, piggery ventilation and cooler systems, automatic pig feeders, piggery heating equipment, and artificial insemination systems. In addition, scientists have replaced the use of antibiotics with organic acids, fermented mash, probiotics, prebiotics, minerals, oligosaccharides, enzymes, herbs/flavors, and protein/amino acids, and have improved management and husbandry techniques. In addition, animal welfare legislation has been aimed at improving the quality of the floors and living space, ensuring that animals have permanent access to fresh water, and setting a minimum weaning age. Finally, the prospects and the possibility of replacing antibiotics in pork production are described, in line with recent research results.