The recent increase in numbers of β-lactamase-producing organisms (BLPO) in respiratory tract infections has been associated with increased failure rates of penicillin therapy. These infections include otitis media, sinusitis, pharyngotonsillitis and pneumonia. The BLPO are Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, pigmented Prevotella and Porphyromonas spp, Bacteroides spp and Fusobacterium spp. The pathogenicity of these BLPO is expressed directly through their ability to cause infections, and indirectly through the production of β-lactamase. The indirect pathogenicity is conveyed not only by surviving penicillin therapy but also by 'shielding' penicillin-susceptible pathogens from the drug. The direct and indirect virulence characteristics of these bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. Proper antimicrobial therapy using such agents combined with surgical drainage and correction of pathology constitute the cornerstone of management of respiratory tract infections.