The prevalence of adult ADHD is estimated to 5.3% and is often comorbid with substance use disorder (SUD) . The odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients without SUD. Methylphenidate (MPH) alleviates ADHD symptoms and is currently considered as a first choice medication. MPH competitively binds and blocks the dopamine (DAT) and norepinephrine (NET) transporters with no or low affinity for the serotonin transporter . This mechanism of action is similar to a cocaine intake, which results in a rapid increase of the synaptic dopamine concentration preferentially in the nucleus accumbens . However, the subjective effects are highly dependent on the rate of input. Oral or IV MPH leads to different effects even when the increase of dopamine concentration is comparable. It is more the change per unit time of the dopamine increase (rapid elevation) that is associated to the perception of euphoria than the increase of dopamine itself . A formulation with a slow rate of delivery will lead to a lower risk of reinforcing effect (euphoria) and abuse than an immediate release formulation. The benefits of MPH in adult ADHD have been demonstrated in open-label prospective studies and in randomized clinical trials. Meanwhile prescribing MPH to patients with comorbid SUD has always been challenging for clinicians. In this presentation, we will address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on the type of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH treatment deserve to be evaluated individually.