This paper is a review of our recent work on the structure and dynamics of the Fe–CO bond in carbonmonoxy myoglobin (MbCO), performed using density functional theory, Car–Parrinello molecular dynamics and hybrid quantum mechanics/molecular mechanics approaches. The results of these investigations have served to shed light onto one of the long standing questions in myoglobin research: whether the protein discriminates the CO ligand with respect to O 2 by distorting the FeCO bond. The calculations show that both in the gas phase and in the protein the Fe–CO bond is essentially linear and therefore exclude the hypothesis that the CO in MbCO is sterically hindered. In contrast, hydrogen bonding between the O 2 ligand and the His64 residue easily explains the protein discrimination for CO.