This chapter briefly explores the principles and applications to the field of toxicology of two computational structural biology techniques: molecular docking and molecular dynamics (MD) simulations. In general, these in silico approaches enable us to do two important things: (1) gain insight into molecular mechanisms of toxicity; and (2) suggest mechanistic hypotheses for experimental validation or refutation. In addition, through the application of inverse docking and pharmacophore/toxicophore mapping, it is possible to identify potential macromolecular targets of toxicants, including off-targets of pharmaceutical agents. Although docking and MD simulations can be used to examine protein–protein and protein–DNA interactions, our focus is on small-molecule toxicants and protein targets.