Antibiotic side effects are approached best from an individual agent perspective rather than from a class-related standpoint. As this article indicates, with the exception of drug fevers and drug rashes, most antibiotic side effects are related to individual agents and not class side effects. Clinicians should view antimicrobial side effects as related to each organ system and be aware that more often a nonmicrobial medication is the explanation for the drug side effect rather than the antimicrobial. Nonantimicrobial medications are the most common cause of drug fever; among antimicrobials, beta-lactams and sulfonamides are the most common causes of drug-induced fevers. Antimicrobial side effects have important implications for the patient, legal and economic implications for the hospital, and medicolegal implications for the physician. Antibiotic side effects that prolong hospitalization in today's managed care environment have important economic implications. Clinicians should be familiar with the most common side effects of the most frequently used antimicrobials, to minimize the potential of having adverse reactions occur in patients. Most adverse events related to antimicrobials are reversible rapidly on cessation of the medication. Irreversible toxicities include aminoglycoside-induced ototoxicity, Stevens-Johnson syndrome, and toxicity secondary to nitrofurantoin. The most common acute fatal drug reactions include hypersensitivity reactions resulting in anaphylaxis or the Stevens-Johnson syndrome and fatal hepatic necrosis secondary to trovafloxacin. Clinicians should eliminate the use of drugs associated with chronic or fatal toxicities because multiple therapeutic alternatives exist for virtually every potential infection.