Staphylococcus aureus is a gram-positive coccus forming grape like clusters performing both aerobic and anaerobic respiration. Most strains of S. aureus ferment mannitol and they form characteristic golden yellow colonies. They produce catalase, coagulase, and extracellular cell clumping factor. Some strains can also produce capsules. It is a major commensal bacterium and a human pathogen that causes a wide range of clinical infections including abscesses of various organs, pneumonia, osteomyelitis, endocarditis, arthritis, and sepsis. S. aureus is the key organism for food poisoning and it is the third most important cause of food borne disorders in the world. We reviewed all the relevant literature available on PubMed, Web of Science, and Google Scholar. We selected different scientific studies and reports published in English language which addressed prevalence, pathogenesis, burden and laboratory diagnosis methods of S. aureus to compile the current review. Staphylococcus aureus has an outstanding ability to acquire resistance to most classes of antimicrobial agents. This successful and adaptable resistance has made treatment and control of staphylococcal infections increasingly difficult. Expression of virulence factors of S. aureus is controlled by bacterial cell density and many environmental factors such as pH, oxygen, and carbon dioxide. There are different mechanisms that microorganisms use to prevent attack by antimicrobial agents. These include limiting uptake of the drug, modification of the drug target, inactivation of the drug, and active efflux of the drug. Specimens collected for diagnosis of S. aureus infection depend on the type of infection. The samples for diagnosis are pus, sputum, blood, feces, vomit and the remains of suspected food, and nasal swab for the detection of carriers. Gram stain, culture, biochemical tests, serological tests and molecular techniques are the common laboratory diagnosis methods. Multidrug resistant S. aureus strains are emerging and current antibiotics are not efficacious against such strains. Both active and passive immunization strategies have thus far failed to show efficacy in humans. Therefore, infection preventive measures, and further research is required to develop vaccines and antibiotics to target this pathogen.