Development of resistance to available antimicrobial agents has been identified in every decade since the introduction of the sulfonamides in the 1930s. Current concerns for management of acute otitis media (AOM) are multi-drug resistant Streptococcus pneumoniae and beta-lactamase producing Haemophilus influenzae and Moraxella catarrhalis. In the USA, amoxicillin remains the drug for choice for AOM. Increasing the current dose to 80 mg/kg/day in two doses provides increased concentrations of drug in serum and middle ear fluid and captures additional resistant strains of S. pneumoniae. For children who fail initial therapy with amoxicillin an expert panel convened by the Centers for Disease Control and Prevention suggested amoxicillin-clavulanate, cefuroxime axetil or intramuscular ceftriaxone. To protect the therapeutic advantage of antimicrobial agents used for AOM, it is important to promote judicious use of antimicrobial agents and avoid uses if it is likely that viral infections are the likely cause of the disease, to implement programs for parent education and to increase the accuracy of diagnosis of AOM. Conjugate polysaccharide pneumococcal vaccines are currently in clinical trial; early results indicate protective levels of antibody can be achieved with a three dosage schedule beginning at 2 months of age. Finally, alternative medicine remedies may be of value for some infectious diseases including AOM; garlic extract is bactericidal for the major bacterial pathogens of AOM but is heat- and acid-labile and loose activity when cooked or taken by mouth.