Antibiotic resistance is an increasing problem worldwide. Much of the antibiotic resistance occurs among community-acquired and nosocomial pulmonary pathogens. Antibiotic resistance may be classified as relative or absolute, which has important therapeutic implications. Considerable misunderstanding exists with regard to the factors that are responsible for antibiotic resistance. Misuse and overuse of antibiotics should be avoided; however, high volume of antibiotic use alone does not result in resistance. Antimicrobial resistance is agent specific and not related to antibiotic class. The antibiotics associated with a high resistance potential include ampicillin, cefamandole, ceftazidime, imipenem, ciprofloxacin, and vancomycin. The use of these antibiotics should be restricted to prevent generalized resistance problems. The substitution on the formulary of ;;vacuum cleaner'' antibiotics, along with effective infection control measures, can eliminate resistance problems in institutions. The key to controlling antibiotic resistance is to selectively use antibiotics with a low resistance potential and restrict those with a high resistance potential.