Critically ill infants are subjected to many painful experiences that, if inadequately treated, can have severe physiological and psychological consequences. Optimal management of pain relies on the adequacy of nurses' assessment; this, however, is complicated by another common condition, agitation. A multidimensional assessment is therefore necessary to adequately identify pain and agitation. The aim of this descriptive study was to identify the cues that nurses caring for critically ill infants use to assess pain and agitation. A questionnaire, developed from the literature, was distributed to all registered nurses (85) working in the neonatal and paediatric intensive care units of an Australian teaching hospital. Questionnaires were completed by 41 nurses (a 57 per cent response rate). Results revealed that, except for diagnosis, there were no significant differences between the cues participants used to assess pain and those to assess agitation. Nurses used numerous cues from various sources: most importantly, their own judgement (99 per cent); the parents' judgement (90 per cent); the infant's environment; documentation (78 per cent), and the infant's cues (70 per cent). These findings demonstrate the relevance of the nurse's role in assessment of pain and agitation in critically ill infants. Nurses used cues specific to the critically ill rather than the less sick infant. Results of this study also show the difficulty of differentiating between pain and agitation. Further research on ways of distinguishing between the construct of pain and agitation needs to be undertaken.