Whereas the majority of individuals in society experiment with drugs and alcohol, only a small subset develops problems or disorders related to such use. Individual difference factors that influence (i.e., either increase or decrease) vulnerability to drug and alcohol use disorders include environmental, trait, and genetic factors. These factors are prime targets for (a) identification of those at high risk to develop problematic use, (b) prevention of transition from social to disordered use, and (c) development of personalized treatments to reduce risks and consequences. The goal of this special section is to highlight translational clinical and preclinical research that focuses on individual differences in environment, traits, and genetics that affect vulnerability to drugs and alcohol. Bringing together researchers who study these risk and protective factors in both nonhuman animal and human models will advance translational approaches in this field through improved collaborations between research laboratories and better translation and backtranslation of models and designs. This special section aims to present reviews and original research addressing these different individual factors and to catalyze future translational research in the field. (PsycInfo Database Record (c) 2020 APA, all rights reserved).