Pain assessment in neonates often presents problems. The problem of inadequate or inaccurate assessment is complicated by issues related to the nature, consistency, and variability of the infant's physiologic and behavioral responses; the reliability, validity, specificity, sensitivity, and practicality of existing neonatal pain measures or measurement approaches; ethical questions about pain research in infants; and uncertainty about the responsibilities of health care professionals in managing pain in clinical settings. Despite these many issues, neonates need to be comfortable and as free of pain as possible to grow and develop normally. Valid and reliable assessment of pain is the major prerequisite for attaining this goal. Issues embodied in neonatal pain responses, measurement, ethical, and clinical considerations are explored. Suggestions for resolving some of these problems are presented.