Neurocritical care bioinformatics is a new field that focuses on the acquisition, storage and analysis of physiological and other data relevant to the bedside care of patients with acute neurological conditions such as traumatic brain injury or stroke. The main focus of neurocritical care for these conditions relates to prevention, detection and management of secondary brain injury, which relies heavily on monitoring of systemic and cerebral parameters (such as blood-pressure level and intracranial pressure). Advanced neuromonitoring tools also exist that enable measurement of brain tissue oxygen tension, cerebral oxygen utilization, and aerobic metabolism. The ability to analyze these advanced data for real-time clinical care, however, remains intuitive and primitive. Advanced statistical and mathematical tools are now being applied to the large volume of clinical physiological data routinely monitored in neurocritical care with the goal of identifying better markers of brain injury and providing clinicians with improved ability to target specific goals in the management of these patients. This Review provides an introduction to the concepts of multimodal monitoring for secondary brain injury in neurocritical care and outlines initial and future approaches using informatics tools for understanding and applying these data to clinical care.