There is and has been continued change in organisms causing infection in the hospital. In the past few years, although Gram-negative bacteria have remained a major cause of mortality, Gram-positive bacteria and fungi have become increasingly important. This has caused organisms such as methicillin-resistant staphylococci, enterococci, Xanthomonas maltophilia and multiply resistant Pseudomonas aeruginosa to be common pathogens. Can this difficult state of affairs be changed by better antimicrobial prescribing practices? Yes and no. Virtually any agent will select MRSA and MRSE since the chromosomal location of the resistance of multiple-antibiotics makes such selection common and explains the rapid rate of the fluoroquinolones as therapy of MRSA. Restriction of oral vancomycin will markedly reduce the pressure to select Enterococcus faecium and thus limit the spread of the organisms and delay transmission of glycopeptide resistance to S. aureus. Judicious use of antibiotics in the intensive care environment will be major factor in "saving" antibiotics for other patients since the ICU patient goes to other parts of the hospital carrying with him/her the baggage of resistant Staphylococcus haemolyticus, klebsiella, P. aeruginosa, acinetobacter, enterobacter, xanthomonas and Pseudomonas cepacia. All of these organisms have the potential to become resistant to the agents heretofore used to treat them and are common in ICU patients.