Open AccessSuccessful vaccine development requires knowing which adjuvants to use and how to formulate adjuvants and antigens to achieve stable, safe and immunogenic vaccines. There is growing literature on immuno-regulatory and adjuvant functions of heat shock proteins (HSPs) in the development of preventive and therapeutic vaccines against cancer and infectious diseases. These extremely conserved molecules associate with antigenic peptides from tumor, virus and intracellular bacteria, present these loaded antigens to both MHC class I and class II molecules and activate specific T cells. This review aims to summarize the data on the HSP roles as the efficient tools in cancer. The ability of heat shock proteins to chaperone peptides (e.g., antigenic peptides); interact with antigen presenting cells (APCs) through a receptor; stimulate APCs to secrete inflammatory cytokines; and mediate maturation of dendritic cells, permit the utilization of these proteins to develop a new generation of prophylactic and therapeutic vaccines against cancers and infectious diseases. Furthermore, some cancers demonstrate elevated levels of HSPs and their expression has been associated with cell proliferation and disease prognosis. New adjuvant development is needed to identify novel combinations of adjuvants and formulations capable of inducing strong, long lasting humoral and cellular immune responses in humans. Numerous challenges remain related to adjuvant development. Among efficient adjuvants, it has been shown that heat shock proteins induce cross-presentation of antigens by dendritic cells (DC) as well as DC maturation. These properties make HSP-antigen complexes good candidates to prime CD8+ T cell responses against tumor-associated antigens. Moreover, these conserved proteins can be used as diagnostic biomarkers in various cancers.