This review article summarized recent advances in the heat-induced antigen retrieval technique with numerous scientific fields in addition to immunohistochemistry. Particularly, proteomics including imaging mass spectrometry, extraction of proteins from formalin-fixed, paraffin-embedded (FFPE) tissues. Some novel approaches such as FFPE tissue-based renal immunopathology based on modified double heating protocols are also introduced in this review for further development. In general, the FFPE tissue housed in pathology worldwide is an invaluable treasure, and the simple method of heat-induced antigen retrieval is the gold key to open the door of this treasure.