In addition to their conventional chaperon activity, numerous studies have reported that heat shock protein 70 (HSP0) exhibit immune properties and especially the capacity (i) to induce the presentation and cross-presentation of associated or client proteins and, (ii) to control myeloid cell activation. Several studies were focused on the identification of HSP70-binding elements that contribute to their immune properties. A general consensus was reached on the nature of the endocytic receptors involved in the internalization of extracellular HSP70 with belong, for most of them, to the innate immunity receptor family. However, the nature of signaling receptors recruited by HSP70 remains unclear, because the stim-ulatory versus regulatory properties of HSP70 remains a subject of debate. Nevertheless, these unique immune properties allowed developing innovative pro-phylactic and therapeutic vaccines, especially in the treatment of cancers and chronic viral infections. Although HSP70 constitute potent vaccine vehicles in different preclinical models, clinical studies remain disappointing. The fact that the immune properties of HSP70 have not been totally clarified may explain their relative efficacy in human. In this review are presented the main immune properties of HSP70 related to the HSP70-binding elements identified to date, and discuss our current knowledge on their intrinsic immune properties.