Personality disorders (PDs) and substance use disorders (SUDs) frequently co-occur both in the general population and in clinical settings. The authors review the recent literature that documents high comorbidity between these two classes of disorders, discuss possible mechanisms of comorbidity, and describe the clinical implications of this comorbidity. Although most attention on comorbidity between PDs and SUDs has focused on antisocial personality disorder (ASPD) and borderline personality disorder (BPD), it is also clear that other PDs (in particular, paranoid, avoidant, and obsessive compulsive PD) are prevalent among those suffering from SUDs. The effect of SUD on PD expression appears to be one of exacerbating PD symptomatology and, in turn, contributing to chronicity. This has important treatment implications in that clinicians must keep in mind the challenges present when planning and implementing treatment for those with both SUD and PD.