The two classes of osteopontin (OPN) receptors identified so far, CD44 and integrins, each have an extensive literature independent of OPN. Multiple activities have been attributed to these receptors, from development to leukocyte and lymphocyte homing and activation. Further investigation is required first to characterize better what biological activities OPN possesses, and then to determine which receptors are responsible for these activities. There are promising therapeutic agents under development for inhibiting integrin function. Some of these biological effects may be the result of inhibiting OPN activity. The opportunities for modulation of CD44 activity and for specific OPN antagonists have yet to be pursued.