Over the past decade, patterns of resistance to antimicrobial agents have changed dramatically, particularly because of the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA), as well as the increasing rate of antimicrobial resistance seen in several species of Gram-negative bacteria. The unique nature of the intensive care unit (ICU) environment makes it a focus for the emergence and spread of many antimicrobial-resistant pathogens. The patients in this setting are commonly exposed to broad-spectrum antimicrobial agents, and opportunities for the cross-transmission of resistant bacteria from patient to patient abound. Not surprisingly, resistance rates have increased for most pathogens associated with nosocomial infections among ICU patients, and rates are almost universally higher among ICU patients than among non-ICU patients. MRSA strains are now spreading in the community, possibly because of antibiotic pressure outside the hospital, but also because of transfer from hospital settings. Such strains are worrisome, particularly the strains carrying the gene for Panton-Valentine leukocidin (PVL), which has been associated with heightened virulence. Managing infections caused by today's pathogens requires avoidance of antimicrobial agent overuse and appropriate selection, dosing and duration of efficacious antimicrobial therapy.