Antibiotic resistance to available antimicrobial agents has been constant since the introduction of the sulfonamides in the 1930s. Multidrug-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae are a concern now because of the importance of these pathogens in infections of the respiratory tract in infants and children. Amoxicillin remains the drug of choice for initial episodes of acute otitis media (AOM) although increase of the dosage schedule to 80 mg/kg/day has been recommended by some investigators. There are 15 additional antimicrobial agents approved by the Food and Drug Administration for the indication of AOM. All approved drugs are clinically effective but some have been suggested to have priority for patients who fail amoxicillin: amoxicillin-clavulanate; an oral cephalosporin such as cefuroxime axetil; and intramuscular ceftriaxone. Management of the child with severe and recurrent disease should include antibiotic prophylaxis but the increased incidence of resistance requires selective use. Prevention of infection may be achieved by innovative techniques for interference with attachment of bacteria to the nasal mucosa such as administration of oligosaccharides in a nasal spray. The currently available polysaccharide pneumococcal vaccines have limited immunogenicity in infants, but the vaccine is useful in children 2 years of age and older who still have recurrent AOM. Children with frequent AOM during the prior respiratory season are candidates also for influenza virus vaccine. If medical management fails to prevent new episodes of AOM in children with severe and recurrent disease, placement of tympanostomy tubes and possible adenoidectomy should be considered.