In the current paper, we describe the challenges in measuring return on investment (ROI) and review published ROI studies on health IT. In addition, given the absence of a robust ROI literature base, we review the general benefits and potential costs of various health IT applications including electronic health records (EHRs), computerized physicians order entry (CPOE) systems, and clinical decision support systems (CDSS). We conclude that articles examining these benefits are much more common than studies examining ROI itself. This trend suggests the early stage of this knowledge base. Additional research utilizing broader perspectives and multidisciplinary techniques will be needed before a better understanding of ROI from health IT is achieved.