Protein-protein interactions play crucial roles in biological processes, especially for heme proteins. Cytochrome b5 (Cyt b5 ) is a typical heme protein, which functions in vivo through various protein-protein interactions. As reviewed herein, the currently revealed interactions associated with Cyt b5 include Cyt b5-Cyt b5 reductase, Cyt b5-Cyt P450, Cyt b5-Cyt c, Cyt b5-myoglobin or hemoglobin, Cyt bs-fusion proteins (glutathione S-transferase, GST, and green fluorescence protein, GFP) , and Cyt b5-tansporters ( sucrose transporter, SUT1,...