Heat shock proteins (HSPs) exist ubiquitously across all species and function as chaperones stabilizing and delivering peptides. Tumor-derived HSP-peptide complex has been known to induce immunity against the original tumor in preclinical studies. HSP-based vaccines work across tumor types and bypass the need for identifying the responsible peptide(s) for inducing immunity. These vaccines are tumor- and patient-specific in that they capture the tumor cells' fingerprints. HSP-based vaccines have been studied in early phase clinical trials, mostly using HSP glycoprotein 96, for various types of malignancies including melanoma, renal cell carcinoma, gastric cancer, pancreatic cancer, low-grade lymphoma, colorectal cancer and chronic myelogenous leukemia. All showed minimal toxicity and potential efficacy. Phase III studies for melanoma and renal cell carcinoma are ongoing. HSP-based vaccines are a novel vaccine preparation with a promising role in cancer management. Further studies to determine the administering strategy and specific indication are warranted.