Antibiotics are used in livestocks not only in case of infections but also in prophylactic treatments to favour growth of animals. They are often added to feed, with a high percentage of unmodified antibiotics reaching intact the environment and constituting new emerging contaminants. Especially in the past, the same antibiotics supplied to animals could also be used in humans. Antibiotics resistance onset can originate inside the animals, in the resistome of the intestine, with a similar mechanism as the antibiotic resistance triggering in humans. Once activated within cattle, antibiotic resistant bacteria and related antibiotic resistance genes can be spread via food, milk and meat, or via manure which can be spread into the environment during fertilization procedures. Antibiotic resistant bacteria and genes of antibiotic resistance can thus reach human beings and the resistance genetic determinants can be included in pathogenic bacteria, vinifying action of antibiotics against those pathogens. The Mediterranean area presents a high density of dairy cattle livestocks and the problem of antibiotic resistance spread is of great concern. It is important to monitor the extent of antibiotic resistance diffusion and the possible consequent ineffectiveness of the known antibiotics against pathogenic bacteria. If from one hand it is of paramount importance to discover new antibiotics active against pathogenic bacteria, although this approach needs time, from the other hand it is mandatory to find new approaches facing with the problems of antibiotic resistance. A One Health approach, focusing on the cooperation of medical and veterinarian staffs, including people operating for environmental safeguard, could represent a valid method to actuate a decrease of the use of antibiotics in cattle livestocks and to operate with a continuous control and a monitoring of the critical points, in order to counteract the challenge of antibiotic resistance. This minireview was focused on antibiotic resistance onset in cattle livestocks in the Mediterranean area, calling attention on the high potential of spread of antibiotic resistance in humans, animals and in the environment, thus evidencing the need of a One Health approach to face with this concern.