Since the introduction of antimicrobial chemotherapy, staphylococci have shown a remarkable propensity to develop drug resistance. As a result, strains have evolved that are resistant to most classes of clinically useful antimicrobial agents. The emergence of these multiply-drug-resistant strains is primarily due to the capture of pre-existent resistance genes. In combination with plasmids and gene transfer mechanisms, mobile genetic elements have been central to the acquisition and dissemination of this resistance. In particular they have played a significant role in the assembly of drug-resistance gene clusters in these multiply-resistant staphylococci.