The integration of neurobiology into ethnographic research represents one fruitful way of doing biocultural research. Based on animal research, incentive salience has been proposed as the proximate function of the mesolimbic dopamine system, the main brain system implicated in drug abuse (Robinson and Berridge 2001). The research presented here examines incentive salience as the mediator of the wanting and seeking seen in drug abuse. Based on field work with adolescents at a school and a drug treatment center in Bogotá, Colombia, this article addresses: 1) the development of a scale to measure the amount of incentive salience felt for drugs and drug use; 2) the results from a risk-factor survey that examined the role of incentive salience and other risk factors in addiction; and 3) the ethnographic results from in-depth interviews with Colombian adolescents examining dimensions of salience in the reported experiences of drug use. Incentive salience proved to be a significant predictor of addicted status in logistic regression analysis of data from 267 adolescents. Ethnographic results indicated that incentive salience applies both to drug seeking and drug use, and confirmed the importance of wanting, a sense of engagement, and shifts in attention as central dimensions of experiences related to drug use.