Hsps were long thought to be cytoplasmic proteins with functions restricted to the intra-cellular compartment. However, an increasing number of observations show that they can be released into the extra-cellular space and can then have a wide variety of affects on other cells. The mechanism of release remains unknown, but may involve the shedding of exosomes, which are vesicles containing cytoplasmic constituents. In the nervous system, it appears that glial cells can release the 70 kD Hsps and that neurons exposed to extra-cellular Hsps are more likely to survive injury than their naïve counterparts. These phenomena have great potential significance in the development of neuroprotective therapeutic strategies utilizing the heat shock protein response.