This article discusses the use of biobehavioral measures as outcomes for healthcare intervention studies. Effect size (ES) values for salivary cortisol, and observation-based measures of pain and agitation are examined. Effects pre to post treatment were assessed separately for nursing home (NH) residents with and without acute psychotic symptoms. This study revealed large positive effects on both pain and agitation measures in the group with acute psychotic symptoms and small-to-medium positive effects on these same measures in the group without acute psychotic symptoms. In both of these groups the ES values were not consistently positive on the cortisol measures. Prior to determining if a measure can be used to estimate minimum clinically important differences, it is essential to consider if the biomarker will be responsive to therapy in the populations and contexts being studied.