The causative pathogens in the majority of mild to moderate upper respiratory tract infections are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Bacterial infections of the respiratory tract are often treated empirically; however, the recent increase in serious infections caused by S. pneumoniae and rising antimicrobial resistance rates have prompted experts to reevaluate the therapeutic approaches to treatment of these infections. Although amoxicillin continues to be considered a first line therapy, some situations warrant alternative therapies. Antimicrobial therapy must provide effective coverage of the potential pathogens, yet issues of compliance must also be addressed to ensure clinical success. Ease of administration, taste and the potential for adverse events are important considerations for the pediatric population. Clinical trials support the use of alternative therapies in the treatment of patients with upper respiratory tract infections.