Personality disorders (PDs) and substance use disorders (SUDs) frequently co-occur in both the general population and in clinical settings. Literature is reviewed documenting high comorbidity between these two classes of disorders, possible mechanisms of comorbidity, and the clinical implications of this comorbidity. Special emphasis is given to antisocial personality disorder (ASPD) and borderline personality disorder (BPD) as these disorders not only co-occur frequently with SUDs in the clinical populations and present clinical challenges, but also because recent research points to etiologic processes that are common to these specific PDs and SUDs. Although most attention on comorbidity between PDs and SUDs has focused on ASPD and BPD, it is also clear that other PDs (in particular, avoidant PD and paranoid PD) are prevalent among those suffering from SUDs.