Molecular chaperone-peptide complexes extracted from tumors (heat shock protein [HSP] vaccines) have been intensively studied in the preceding two decades, proving to be safe and effective in treating a number of malignant diseases. They offer personalized therapy and target a cross-section of antigens expressed in patients' tumors. Future advances may rely on understanding the molecular underpinnings of this approach to immunotherapy. One property common to HSP vaccines is the ability to stimulate antigen uptake by scavenger receptors on the antigen-presenting cell surface and trigger T-lymphocyte activation. HSPs can also induce signaling through Toll-Like receptors in a range of immune cells and this may mediate the effectiveness of vaccines.