Fecal glucocorticoid metabolite analyses are increasingly being used by a variety of scientists (e.g., conservation biologists, animal scientists) to examine glucocorticoid (i.e., stress hormone) secretion in domestic and wild vertebrates. Adrenocortical activity (i.e., stress response) is of interest to conservation biologists because stress can alter animal behavior, reduce resistance to disease, and affect population performance. The noninvasiveness of fecal-based assessments is attractive, particularly when studying endangered species, because samples can often be obtained without disturbing the animal. Despite such advantages, many confounding factors inhibit the utility of this technique in addressing conservation problems. In particular, interpretation of fecal glucocorticoid metabolite (FGM) measures may be confounded by the length of time animals are held in captivity, normal seasonal and daily rhythms, body condition, sample storage and treatment techniques, diet of the animal, assay selection, animal status (i.e., social ranking, reproductive status), sample age and condition, and sample mass. Further complicating interpretation and utility of these measures is the apparent species-specific response to these factors. The purpose of this paper is to discuss the factors that confound interpretation of FGM measures, summarize research that addresses these issues, and offer an agenda for future research and interpretation. We urge conservation biologists to carefully consider confounding factors and the relationship between FGM secretion and population performance and biological costs when investigating effects of environmental and human-induced disturbances on wildlife. The crisis nature of many decisions in conservation biology often requires decisions from limited data; however, confirmatory results should not be posited when data are incomplete or confounding factors are not understood. Building reliable databases, and research with surrogate species when possible, will aid future efforts and enhance the utility of FGM assays.