A significant literature suggests that youth diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) are at increased risk for later depression relative to youth without ADHD. Youth with co-occurring ADHD and depression experience more serious impairments and worse developmental outcomes than those with either disorder alone, including increased rates of suicidal ideation and suicide completion. Despite these very serious outcomes, few studies have examined the mechanisms underlying the relationship between ADHD and depression in youth. The present study examined emotion regulation (ER) as a mediator of the relationship between ADHD and depressive symptoms in 69 youth between the ages of 10 and 14, with (n = 37) and without (n = 32) ADHD. Parent and youth ratings of depressive symptoms and ER were collected. Youth with ADHD reported significantly more depressive symptoms and poorer ER ability relative to youth without ADHD. ER fully mediated the relationship between ADHD and depressive symptoms. Limitations and clinical implications are discussed.