Bacterial resistance to antibiotics and other harmful substances ͑e.g., heavy metals͒ often occurs through genes carried on plasmids: autonomously replicating DNA elements that are nearly ubiquitous in bacterial populations. Individual plasmids can sometimes include multiple genes conferring resistance to a variety of antibiotics. Also, plasmids can effectively spread within and among bacteria populations and species through conjugation ͑cell-to-cell horizontal transfer͒. Together, these features create the capacity for rapid spread of multiple drug resistance in bacteria. Furthermore, plasmid-borne mechanisms ͑e.g., postsegregational killing͒ often exist to ensure that vertical transfer ͑plasmid inherit-ance͒ is reliably maintained across host-cell generations. For these reasons, plasmid biology has undoubtedly contributed to the current crisis of ineffective antibiotic therapy.