The impact of therapeutic hypothermia (TH) on long-term neurological outcome is still controversial. Data on the effects of TH on brain homeostasis are mostly derived from experimental research. Invasive multimodal neuromonitoring techniques may provide additional insight into pathophysiological changes associated with primary or secondary brain injury in humans. In this study we describe the principles of multimodal neuromonitoring and its potential in the clinical setting of TH. We call for more research using multimodal neuromonitoring techniques in patients undergoing TH to optimize cooling and rewarming strategies.