Most acute orofacial infections are of odontogenic origin. In normal hosts, however, they usually do not occur without some type of predisposing condition. Early recognition and management of acute orofacial infections is critical, because rapid systemic involvement can occur, especially in children. Antimicrobial therapy has an essential role in the management of these infections. If it is initiated before surgery, it can shorten the period of infection and minimize associated risks. The etiology of odontogenic infections is usually attributed to the endogenous flora of the mouth, and not to the introduction of non-resident bacteria. Odontogenic infections are typically polymicrobial; however, anaerobes generally outnumber aerobes by at least four fold. The penicillins have historically been used as the first-line therapy in these cases, but increasing rates of resistance have lowered their usefulness. Bacterial resistance to this class of agents is predominately achieved through the production of beta-lactamases. Clindamycin, because of its broad spectrum of activity and resistance to beta-lactamase degradation, is an attractive first-line therapy in the treatment of odontogenic infections.