Drugs differ in their ability to eradicate various pathogens from the middle-ear cavity during acute otitis media (AOM), and these differences clearly affect clinical outcome. Outcome is derived from differences in the association between concentrations of the drugs at the site of infection and the antimicrobial effect (termed pharmacodynamics). These differences are even more marked in the present era of antimicrobial resistance. However, since AOM is a self-limiting disease in most cases, difference in clinical outcome is more difficult to ascertain than that of bacteriological outcome, which is measured within 3-5 days. A favourable clinical outcome regardless of the bacteriological effect of the drug can result in false optimism when less-effective antibiotic drugs are used. Inappropriate study design and manipulation of clinical results add to this confusion. In this review we attempt to highlight the evidence regarding bacteriological response to antibiotics in AOM and to draw attention to potential flaws that may mislead clinicians.