Illicit drug use remains a pervasive problem despite decades of research documenting its harmful effects. This chapter discusses how positive and negative drives work together to escalate the transition to addiction. We detail the invaluable contributions of animal models that have improved the ways in which we think about and treat addiction. We discuss how rat ultrasonic vocalizations (USVs) provide a powerful analog to self-reports given by addicts. We review the conceptual framework of the opponent-process model of addiction and discuss how USVs provide new insight as to the time points when positive and negative affective states manifest throughout addiction. We review evidence that links drug-evoked USVs to specific neuronal structures, transmitter systems and circuits. We conclude by discussing the value of utilizing noninvasive and ethologically relevant USVs in studying substance use disorders as well as how the amassed data provide new insight into relationships between affect and addiction.