In this article, a preliminary conceptual framework is presented for exploring nursing interventions and research aimed at improving care of the unconscious brain-injured patient during the early subacute phase of brain injury. The cue-response framework presented is derived from multidisciplinary sources and has specific clinical relevance to critical care nurses caring for unconscious brain-injured patients. A key aspect of this framework is the attention focused on the timing of nursing interventions in response to how nurses interpret the physical, physiological, and secondary cues they observe when caring for comatose patients. A case exemplar is used to present one example of how this framework may be used in the clinical setting.