Abstract: Staphylococcus aureus (S. aureus) is a gram positive organism that serves as an opportunistic pathogen and frequent colonizer of the epithelium causing severe diseases in human and animals. The widespread use of antibiotics both in human and Veterinary medicine resulted in the emergence of resistant strains of S. aureus. Methicillin-resistant Staphylococcus aureus (MRSA) is a common bacterial pathogen responsible for a variety of infections. Resistance to methicillin is determined by the mecA gene, which encodes the low-affinity penicillin-binding protein PBP 2. Lately, new methicillin resistance gene, mecC has been discovered from humans, animals and food products. MRSA infection was first considered hospital-associated (HA-MRSA) and community-associated MRSA (CA-MRSA) infections. However, another group emerged known as livestock-associated MRSA (LA-MRSA). The isolation of MRSA from different species, food products and the environment raised concern on the role of animals particularly livestock and wildlife in the epidemiology of MRSA. The spatial distribution of MRSA indicates interspecies transmission and colonization of different populations. This review summarizes the epidemiology, current knowledge, genetic mechanisms, and transmission pattern of MRSA, and colonization.