Studying a concept as complex as moral distress is an ongoing challenge for those engaged in empirical ethics research. Qualitative studies of nurses have illuminated the experience of moral distress and widened the contours of the concept, particularly in the area of root causes. This work has led to the current understanding that moral distress can arise from clinical situations, factors internal to the individual professional, and factors present in unit cultures, the institution, and the larger health care environment. Corley et al. (2001) was the first to publish a quantitative measure of moral distress, and her scale has been adapted for use by others, including studies of other disciplines (Hamric and Blackhall 2007; Schwenzer and Wang 2006). Other scholars have proposed variations on Jameton's core definition (Sporrong et al. 2006, 2007), developing measures for related concepts such as moral sensitivity (Lutzen et al. 2006), ethics stress (Raines 2000), and stress of conscience (Glasberg et al. 2006). The lack of consistency and consensus on the definition of moral distress considerably complicates efforts to study it. Increased attention by researchers in disciplines other than nursing has taken different forms, some problematic. Cultural differences in the role of the nurse and understanding of actions that represent threats to moral integrity also challenge efforts to build a cohesive research-based understanding of the concept. In this paper, research efforts to date are reviewed. The importance of capturing root causes of moral distress in instruments, particularly those at unit and system levels, to allow for interventions to be appropriately targeted is highlighted. In addition, the issue of studying moral distress and interaction over time with moral residue is discussed. Promising recent work is described along with the potential these approaches open for research that can lead to interventions to decrease moral distress. Finally, opportunities for future research and study are identified, and recommendations for moving the research agenda forward are offered.