Making “greener” chemicals involves maximizing resource efficiency and eliminating or reducing hazards to human health and environmental systems. This chapter presents a review of various tools used in chemical design and predictive toxicology as a practical guide for chemists early in the molecular design process to deal with potential concerns on the front end of synthesis or development. A summary of concepts that can be applied in engineering chemicals that are less likely to be absorbed or biologically active is discussed along with the current milieu of software tools used for toxicity prediction. In this context, the challenges that remain in greener molecular design related to computational toxicology are highlighted. Based on these analyses, a proposed ideal green molecular design tool is outlined.