We read with great interest the comments from Motosko and colleagues (2012) regarding our paper, in which we reported that insulin-like growth factor-1 (IGF-1) was not associated with delirium in our prospective study of critically ill patients (Morandi et al., 2011). Based on these results and those of the other four published studies examining IGF-1 and delirium, we take issue with the statement that a large body of evidence supports IGF-1's role in delirium pathogenesis. As pointed out by Adamis and Meagher (2011) in their recent systematic review, these five studies were small and produced conflicting results, with only three of the five finding an association between IGF-1 and delirium. Important differences in the patients studied may explain, in part, the conflicting results. Investigations of older medical inpatients who were not critically ill found IGF-1 to be associated with delirium, but neither a study of hip surgery patients (Lemstra et al., 2008) nor our study of intensive care unit (ICU) patients found an association. The relative importance of IGF-1 to delirium might be diminished during critical illness given that a multitude of risk factors are involved in the pathogenesis of delirium in this vulnerable population. On average, medical ICU patients are subject to more than ten delirium risk factors; changes in IGF-1 in this setting might therefore contribute less to delirium than in other settings.