Abrupt deprivation of substrates to neuronal tissue triggers a number of pathological events (the “ischemic cascade”) that lead to cell death. As this is a process of delayed neuronal cell death and not an instantaneous event, several pharmacological and non-pharmacological strategies have been developed to attenuate or block this cascade. The most promising neuroprotectant so far is therapeutic hypothermia and its beneficial effects have inspired researchers to further improve its protective benefit by combining it with other neuroprotective agents. This review provides an overview of all neuroprotective strategies that have been combined with therapeutic hypothermia in rodent models of focal cerebral ischemia. A distinction is made between drugs interrupting only one event of the ischemic cascade from those mitigating different pathways and having multimodal effects. Also the combination of therapeutic hypothermia with hemicraniectomy, gene therapy and protein therapy is briefly discussed. Furthermore, those combinations that have been studied in a clinical setting are also reviewed.