The reaction catalyzed by the nitrogenase enzyme involves breaking the stable triple bond of the dinitrogen molecule and is consequently considered among the most challenging reactions in biology. While many aspects regarding its atomic mechanism remain to be elucidated, a kinetic scheme established by David Lowe and Roger Thorneley has remained a gold standard for functional studies of the enzyme for more than 30 years. Recent three-dimensional structures of ligand-bound states of molybdenum- and vanadium-dependent nitrogenases have revealed the actual site of substrate binding on the large active site cofactors of this class of enzymes. The binding mode of an inhibitor and a reaction intermediate further substantiate a hypothesis by Seefeldt, Hoffman, and Dean that the activation of N2 is made possible by a reductive elimination of H2 that leaves the cofactor in a super-reduced state that can bind and reduce the inert N2 molecule. Here we discuss the immediate implications of the structurally observed mode of binding of small molecules to the enzyme with respect to the early stages of the Thorneley-Lowe mechanism of nitrogenase. Four consecutive single-electron reductions give rise to two bridging hydrides at the cluster surface that can recombine to eliminate H2 and enable the reduced cluster to bind its substrate in a bridging mode.