Recurrent acute otitis media occurs during the first several years of life in approximately 20 to 30% of the pediatric population. A clinical challenge closely related to recurrent otitis media is persistent otitis media, manifested by persistence during antimicrobial therapy of symptoms and signs of middle ear infection (treatment failure) and/or relapse of acute otitis media within 1 month of completion of antibiotic therapy. Recurrent and persistent otitis media infections are early childhood problems with identifiable risk factors. Differentiation of these infections from otitis media with effusion is important in avoiding misdiagnosis and overtreatment with antibiotics. The predominant pathogens of recurrent and persistent acute otitis media are antibiotic-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae. A working group convened by the Centers for Disease Control recommended three antibiotics for the treatment of recurrent and persistent acute otitis media: (1) amoxicillin/clavulanate in combination with amoxicillin (high dose amoxicillin regimen, 80 to 90 mg/kg/day); (2) cefuroxime axetil (standard dose, 30 mg/kg/day); and (3) ceftriaxone (possibly requiring up to three injections to optimize clinical success). Other antibiotics were considered suboptimal or had accumulated insufficient data upon which to base a judgment. Conclusions. Optimal management of recurrent and persistent acute otitis media is a clinical challenge. Accurate diagnosis of acute otitis media is the first step in optimal management. Selection of appropriate antibiotic therapy should take into account the major pathogens (S. pneumoniae, H. influenzae and Moraxella catarrhalis) and the occurrence of antibiotic resistance.