Toxicology is required to design safer chemicals, for planning safer chemical synthesis, and to ensure that industrial processes employ safer, healthier, and sustainable chemistries. The principles of green chemistry provide a comprehensive framework to guide this vision by emphasizing a holistic, systems-based approach that acknowledges the inherent hazard associated with all molecules and products. Toxicology provides the theoretical and practical tools to profile the likely behavior of a molecule in living systems based on its physicochemical attributes using computational in silico approaches, in vitro assays at the molecular and cellular levels, and information gleaned from in vivo testing in appropriate test organisms. Molecular design for hazard reduction requires incorporating 21st century toxicology insight to inform synthetic chemists, process engineers, and all scientists, to approach a utopian dream of zero risk from chemicals, realizing that zero hazard is only asymptotically approachable. The development and advancement of computational toxicology, characterizing mechanisms of toxicity using genomics and high-throughput assays, coupled with advancements in chemoinformatics, has augmented the ability to identify and document adverse outcome pathways for known and putative atoms, molecules, compounds, and materials.