The simultaneous presence of a substance use disorder (SUD) along with a psychiatric disorder represents a challenge to the clinician. The self-medication hypothesis suggests that drugs of abuse are used as a means of alleviating the distress associated with the mental disorder. Borderline Personality Disorder (BPD) and Attention Deficit/Hyperactivity Disorder (ADHD) show high comorbidity with substance use disorders, with 40%-60% of patients with the former and 9%-30% of adults with the latter also have an SUD. It is clear that these comorbidities seriously complicate both the detection and the treatment, in as much as the presenting disorder can mask the other, the upshot of which all to frequently the substance abuse or BPD and ADHD remain untreated. SUDs tend to increment the chronicity of BDP and ADHD, and vice versa. Differential diagnosis between BDP and ADHD is complex as some symptoms such as impulsivity, distractibility and low self-esteem are common to both disorders. The co-occurrence of ADHD and BPD further complicates matters, particularly when comorbid with an SUD. Accurate diagnosis and identification of all mental disorders present is essential for effective treatment. Psychostimulants have been found to be effective in the treatment of adults with ADHD, and psychological treatments have been identified for the treatment of both ADHD and BPD, but effective pharmacological treatment of BDP remains elusive. Further research is required to clarify the relationship between ADHD, BPD and substance abuse, and to identify optimal psychopharmacological and psychological treatment for ADHD and BPD when comorbid with an SUD.