Vulnerability to initiate use of psychoactive drugs as well as relapse to drug-seeking in patients with established substance use disorders are precipitated by behavioral disinhibition or impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to negative consequences) and attentional bias toward drug cues (cue reactivity). These behavioral phenotypes are not independent mechanistically nor neurobiologically, and preclinical analyses have demonstrated the complex nature of the interactions between these interlocked phenotypic behaviors, including aspects of their shared neurobiology and circuitry. This chapter focuses on impulsivity and drug-seeking behaviors from a preclinical perspective and summarizes studies exploring the impact of substances of abuse in the context of the neurobiology of impulsivity and drug-seeking behaviors in rodents.