The evaluation of nontoxic-appearing, young, febrile children has been a subject of considerable debate. Of young, nontoxic-appearing children aged 3 to 36 months with temperatures of 39 degrees C or more and no clear source, approximately 2% to 3% have occult bacteremia. Of these bacteremias, approximately 90% are caused by S. pneumoniae, 5% by nontyphoidal Salmonella sp., and 1% by N. meningitidis. Most children with occult pneumococcal bacteremia improve spontaneously, but approximately 25% of untreated patients have persistent bacteremia or develop new focal infections, including 3% to 6% who develop meningitis. Occult meningococcal bacteremia, although rare, has frequent complications, including meningitis in approximately 40% and death in approximately 4%. Less is known about the natural history of untreated occult nontyphoidal Salmonella bacteremia. Empiric antibiotic treatment of children with occult bacteremia decreases the rate of complications, including meningitis. Few disagree that febrile, young children at risk for occult bacteremia require a careful clinical evaluation and close follow-up. The benefits of laboratory screening and selective empiric antibiotic treatment of febrile children at risk for occult bacteremia have to be weighed against the costs of screening tests and blood cultures, inconvenience, temporary discomfort to patients, risk for side effects of antibiotics, and the role of antibiotics in the development of bacterial resistance. Although great debate exists concerning the role of empiric antibiotics, a strategy for obtaining blood cultures and empirically administering antibiotics on the basis of an increased ANC, in addition to close clinical follow-up, may be effective in reducing the frequency and severity of uncommon but adverse sequelae. A highly effective S. pneumoniae bacterial conjugate vaccine will soon be available, which will benefit all children, and will alter the ways that clinicians evaluate fully immunized young, febrile children.