Construction of nitrogen-nitrogen bonds involves sophisticated biosynthetic mechanisms to overcome the difficulties inherent to the nucleophilic nitrogen atom of amine. Over the past decade, a multitude of reactions responsible for nitrogen-nitrogen bond formation in natural product biosynthesis have been uncovered. On the basis of the intrinsic properties of these reactions, this Review classifies these reactions into three categories: comproportionation, rearrangement, and radical recombination reactions. To expound the metallobiochemistry underlying nitrogen-nitrogen bond formation reactions, we discuss the enzymatic mechanisms in comparison to well characterized canonical heme-dependent enzymes, mononuclear nonheme iron-dependent enzymes, and nonheme di-iron enzymes. We also illuminate the intermediary properties of nitrogen oxide species NO2-, NO+, and N2O3 in nitrogen-nitrogen bond formation reactions with clues derived from inorganic nitrogen metabolism driven by anammox bacteria and nitrifying bacteria. These multidimentional discussions will provide further insights into the mechanistic proposals of nitrogen-nitrogen bond formation in natural product biosynthesis.