Since the marketing of anti-depressants these compounds have been used for the treatment of a wide variety of psychiatric and non-psychiatric disorders. To sum just a few: peptic ulcers, migraine, enuresis, narcolepsy, ADHD, urinary stress incontinence, bulimia, neuropathy, cardiac arrhythmia, anxiety disorders, obsessive compulsive disorders etc. ADHD in adults is a clinical diagnosis that can be reliably made. Psychostimulants are the most effective drugs in the treatment of ADHD with impressive effects sizes that are in adults quit similar to those reported in meta-analyses of child and adolescent clinical trials. Stimulants are both safe and effective and are therefore the first line choice for the treatment of ADHD in adults. However, a subset of patients is non-responder or experience adverse effects such as: dysphoria, anxieties, anorectic effects or an exacerbation of seizures. This restricts the use of stimulants in these patients. Moreover, adults with ADHD often show comorbid disorders (depression, anxieties, tics, drug abuse and somatic comorbidity) for which stimulants may be inappropriate. A critical review of controlled clinical trials with antidepressants in adults with ADHD will be presented. This review shows that, in contrast to the treatment of depressive disorders where receptor binding profiles and specific monoamine reuptake inhibition does not predict a clinical response, in ADHD the pharmacological properties of the specific antidepressant is most probably related to efficacy. Only eight trials of good quality were found. Effectsizes are smaller than with stimulants.