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Introduction: The objective of this study was to evaluate the efficacy of the most commonly used antimicrobial treatments in odontogenic infections in children and adolescents on the basis of pharmacokinetic/ pharmacodynamic (PK/PD) criteria., Methods: Unbound drug plasma concentration-time curves were simulated with mean population pharmacokinetic parameters of amoxicillin, co-amoxiclav, cefuroxime axetil, spiramycin, clindamycin, azithromycin, and metronidazole. For drugs showing time-dependent antibacterial killing, the time above MIC90 of the pathogens studied was calculated (T>MIC). For drugs with concentration-dependent bactericidal activity, the area under the concentration-time curve (AUC)/MIC90 ratio was calculated., Results: Adequate efficacy indexes (T>MIC>40%) against all the microorganisms examined with the exception of Veillonella spp. were obtained with co-amoxiclav (80 mg/kg/day). Clindamycin (40 mg/kg/day) obtained adequate PK/PD indexes except for Lactobacillus, Actinobacillus actinomycetemcomitans, penicillin-resistant Peptostreptococcus, and Eikenella corrodens. High-dose amoxicillin yielded unsatisfactory results against many bacterial species. Azithromycin and metronidazole showed inadequate efficacy indexes against the majority of pathogens studied (AUC/MIC90<25)., Conclusion: When antibiotic therapy is needed for odontogenic infections in children and adolescents, the most active empirical therapeutic choice is co-amoxiclav with high doses of amoxicillin. Clindamycin can be used as an alternative option. These results should be confirmed in clinical trials, in which the PK/PD approach could be useful for the design and assessment of results.