%X Living organisms are the most complex chemical system known to exist, yet exploit only a small constellation of universally conserved metabolites to support indefinite evolution. The conserved chemical simplicity belying biological diversity strongly indicates a unified origin of life. Thus, the chemical relationship between metabolites suggests that a simple set of predisposed chemical reactions predicated the appearance of life on Earth. Conversely, if prebiotic chemistry produces highly complex mixtures, this then implies that the feasibility of elucidating life’s origins is an insurmountable task. Prebiotic systems chemistry, however, has recently been exploiting the chemical links between different metabolites to provide unprecedented scope for exploration of the origins of life, and an exciting new perspective on a 4 billion-year-old problem. At the heart of the systems approach is an understanding that individual classes of metabolites cannot be considered in isolation. This review highlights several recent advances suggesting that the canonical nucleotides and proteinogenic amino acids are predisposed chemical structures. %A S Islam %A MW Powner %J Chem %O This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. %L discovery1546013 %V 2 %D 2017 %N 4 %K Origins of life, prebiotic chemistry, systems chemistry, predisposed chemistry, RNA, nucleotides, amino acids, sugars, metabolism, crystallization %T Prebiotic Systems Chemistry: Complexity Overcoming Clutter %P 470-501