N–O σ bonds containing compounds are versatile substrates for organic synthesis in presence of transition metal catalysis. Their ability to react through both ionic (oxidative addition, formation of metallanitrene, nucleophilic substitution) and radical pathways (single electron transfer, homolytic bond scission) have triggered the development of a large scope of synthetic methodologies, in particular towards the synthesis of nitrogen containing compounds. In this review, we discuss the different mode of activation of N–O bonds in presence of transition metal catalysts, emphasizing the experimental and computational mechanistic proofs in the literature to help designing new synthetic pathways.