In recent years, extended ESBL and carbapenemase producing Gram negative bacteria have become widespread in hospitals, community settings and the environment. This has been triggered by the few therapeutic options left when infections with these multi-drug resistant organisms occur. The emergence of resistance to colistin, the last therapeutic option against carbapenem-resistant bacteria, worsened the situation. Recently, animals were regarded as potent antimicrobial reservoir and a possible source of infection to humans. Enteric Gram negative bacteria in animals can be easily transmitted to humans by direct contact or indirectly through the handling and consumption of undercooked/uncooked animal products. In the Mediterranean basin, little is known about the current overall epidemiology of multi-drug resistant bacteria in livestock, companion, and domestic animals. This review describes the current epidemiology of ESBL, carbapenemase producers and colistin resistant bacteria of animal origin in this region of the world. The CTX-M group 1 seems to prevail in animals in this area, followed by SHV-12 and CTX-M group 9. The dissemination of carbapenemase producers and colistin resistance remains low. Isolated multi-drug resistant bacteria were often co-resistant to non-beta-lactam antibiotics, frequently used in veterinary medicine as treatment, growth promoters, prophylaxis and in human medicine for therapeutic purposes. Antibiotics used in veterinary medicine in this area include mainly tetracycline, aminoglycosides, fluoroquinolones, and polymyxins. Indeed, it appears that the emergence of ESBL and carbapenemase producers in animals is not related to the use of beta-lactam antibiotics but is, rather, due to the co-selective pressure applied by the over usage of non-beta-lactams. The level of antibiotic consumption in animals should be, therefore, re-considered in the Mediterranean area especially in North Africa and western Asia where no accurate data are available about the level of antibiotic consumption in animals.