Osteopontin (OPN) is a protein that is widely expressed and will likely have multiple biological functions based on structural modifications of the protein and the local environments in which it is expressed. Evidence is accumulating that OPN plays a role in cells derived from monocytes, including macrophages and osteoclasts. Presently there is strong evidence that OPN can activate the migration and adhesion of many cells in vitro and, therefore, may contribute to the accumulation of cells at sites of inflammation in vivo. The possibility exists that OPN does more than simply mediate the accumulation of cells; studies are needed that evaluate activating or inhibitory signals induced by OPN. In addition, more studies are required to understand OPN's function in normal and disease states.