Inflammation within the central nervous system often accompanies ischemia, trauma, infection, and other neuronal injuries. The immune system is now recognized to play a major role in neuronal cell death due to microglial activation, leukocyte recruitment, and cytokine secretion. The participation of heat shock proteins (Hsps) in the immune response following in brain injury can be seen as an attempt to correct the inflammatory condition. The Hsps comprise various families on the basis of molecular size. One of the most studied is Hsp70. Hsp70 is thought to act as a molecular chaperone that is present in almost intracellular compartments, and function by refolding misfolded or aggregated proteins. Hsps have recently been studied in inflammatory conditions. Hsp70 can both induce and arrest inflammatory reactions and lead to improved neurological outcome in experimental brain injury and ischemia. In this review, we will focus on underlying inflammatory mechanisms and Hsp70 in acute neurological injury.