Oral Diseases (2011) 17, 129–142 Osteoclasts are cells essential for physiologic remodeling of bone and also play important physiologic and pathologic roles in the dentofacial complex. Osteoclasts and odontoclasts are necessary for tooth eruption yet result in dental compromise when associated with permanent tooth internal or external resorption. The determinants that separate their physiologic and pathologic roles are not well delineated. Clinical cases of primary eruption failure and root resorption are challenging to treat. Mineralized tissue resorbing cells undergo a fairly well characterized series of differentiation stages driven by transcriptional mediators. Signal transduction via cytokines and integrin‐mediated events comprise the detailed pathways operative in osteo/odontoclastic cells and may provide insights to their targeted regulation. A better understanding of the unique aspects of osteoclastogenesis and osteo/odontoclast function will facilitate effective development of new therapeutic approaches. This review presents the clinical challenges and delves into the cellular and biochemical aspects of the unique cells responsible for resorption of mineralized tissues of the craniofacial complex.