Psychopathy and depression have rarely been studied together despite relatively high rates of both in court-referred adolescent samples. To determine if youth high in psychopathy and depression experience more psychosocial difficulties, the current study examined psychopathy and depression in 103 adolescent offenders using two well-validated assessments: The Psychopathy Checklist−Youth Version (PCL−YV; Forth, Kosson, & Hare, 1996/2003) and the depression scale of the Adolescent Psychopathology Scale (APS; Reynolds, 1998). Findings showed that psychopathy and depression interact to statistically predict much higher levels of anger, aggression, interpersonal problems, and substance use. Implications for these findings include that youth who are high in psychopathy and come in contact with the law are also at high risk for numerous problems. Clinical implications driven from the current findings are that assessment and treatment programs in juvenile justice settings should be tailored and systematized to address externalizing and internalizing symptoms in youth and also to consider the co-occurrence of the two. Juvenile justice systems might also benefit from developing clinical practices that require assessment and treatment units to undergo program training to ensure that they (a) account for possible co-occurring effects of commonly assessed disorders and (b) adequately treat complex youth mental health problems with customized treatment programs. Such training would allow for more effective treatment affording youth greater opportunities to succeed in society.