Multiple studies have shown that pharmacologic treatments for attention-deficit hyperactivity disorder (ADHD), especially stimulants, are generally effective. There is yet a paucity of empirical data, however, for some common clinical conditions overlooked in the ADHD treatment guidelines. Some examples include: in cases of first line treatment failure, it is unclear whether switching from one type of stimulant to another is beneficial. In cases of comorbid ADHD and severe aggressive/disruptive behavior in children, it is unclear whether the best first-line treatment is stimulants or atypical antipsychotics like risperidone. In cases of ADHD with comorbid anxiety disorders, there is no clear evidence regarding optimal treatment. The objectives of this article are to review these issues and propose possible answers for such clinical dilemmas.