This is the accepted manuscript. It is currently embargoed pending publication. ; Cellular metabolism assembles in a structurally highly conserved, but functionally dynamic system, known as the metabolic network. This network involves highly active, enzyme-catalysed metabolic pathways that provide the building blocks for cell growth. In parallel, however, chemical reactivity of metabolites and unspecific enzyme function give rise to a number of side products that are not part of canonical metabolic pathways. It is increasingly acknowledged that these molecules are important for the evolution of metabolism, affect metabolic efficiency, and that they play a potential role in human disease - age-related disorders and cancer in particular. In this review we discuss the impact of oxidative and other cellular stressors on the formation of metabolic side products, which originate as a consequence of (i) chemical reactivity or modification of regular metabolites, (ii) through modifications in substrate specificity of damaged enzymes, and (iii) through altered metabolic flux that protects cells in stress conditions. In particular oxidative and heat stress conditions are causative of metabolite and enzymatic damage and thus promote the non-canonical metabolic activity of the cells through an increased repertoire of side products. On basis of selected examples, we discuss the consequences of non-canonical metabolic reactivity on evolution, function and repair of the metabolic network. ; Work in the Ralser lab is funded from the Wellcome Trust (RG 093735/Z/10/Z), the ERC (Starting grant 260809). Markus A. Keller is supported by the Austrian Science Funds by an Erwin Schr?dinger postdoctoral fellowship (FWF, J 3341). Markus Ralser is a Wellcome Trust Research Career Development and Wellcome-Beit Prize fellow.