Antimicrobial treatment of otolaryngologic infections can be empiric, supercalculated empiric, or organism-specific. In many instances, it merely is empiric by the epidemiologically established knowledge of the bacterial spectrum for a given infection. Current microbial diagnostic procedures (eg, Gram staining, rapid antigen detection tests, serodiagnostics, nucleic acid amplification procedures, and culture) are analyzed. Direct Gram staining of a swab can be incorporated in the office setting and allows differentiation of the most common pathogens (supercalculated empiric therapy). By this method, treatment can be instituted more specifically with a narrowspectrum antibiotic, and thereby reducing the risk for adverse reactions, costs, and development of resistance. Furthermore, the regional appearance of more resistant gram-positive organisms, as the penicillin-resistant pneumococci or erythromycin-resistant Group A β-hemolytic streptococci and aminopenicillin- resistant Haemophilus influenzae, leads to insecurity with traditional empiric treatment regimens. Current strategies for empiric, supercalculated empiric, and organism-specific therapy are given for various otolaryngologic infections with respect to regional resistance patterns.