Over the past 100 years, medical care for animal diseases has evolved significantly. The purpose of this paper is to review the rational use of veterinary medicines and their current status in Ethiopia. Veterinary drugs are used rationally or irrationally in the livestock sector for therapeutic, prophylactic, and growth-promoting drugs, food preservation and processing, stress control in slaughterhouses prior to slaughter, and reproductive control. Rational use of drugs is the use of the right drug, in the right amount, at the right cost, and at the right time. Irrational use of veterinary drugs is a major problem when used in food-producing animals. Reasons for irrational drug use include poor communication between owners and professionals, inadequate training and education of veterinary graduates, demands from owners, and lack of diagnostic equipment. Irrational use of drugs can negatively impact public health, including: decreased quality of drug therapy leading to increased mortality and morbidity; increased risk of undesirable effects (emergence of drug resistance and side effects); waste of resources leading to decreased availability of other important drugs; increased costs; adverse, sometimes increased, in some cases lethal, effects, and so on. To promote the rational use of drugs, WHO has announced 12 core interventions. In Ethiopian veterinary clinics, there were problems with correct diagnosis, low prescriber education levels, the presence of a small number of essential drugs, the absence of a standard veterinary drug list, and inappropriate drug use leading to irrational drug use. Therefore, attention should be paid to proper diagnosis, educational status of prescribers, different types of drugs, and meeting all the customs of the national veterinary drug lists and guidelines..