Driving a car is vital for the functional autonomy of patients to take part in activities of daily living. Both psychopathologic symptoms and psychopharmacologic treatment may impair driving ability. This article provides a systematic review of published studies (1980-2011) on commonly prescribed newer antidepressants and driving performance. A total of 21 studies could be included in the review, indicating that there is a lack of controlled patient studies. Investigations on newer antidepressants were frequently undertaken in healthy subjects focusing on acute or subchronic effects of application, predominately in young male participants, with dosages usually given in an ambulatory setting. No data, according to selection criteria, were found with respect to agomelatine, duloxetine, bupropion and viloxazine. There is evidence that the SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline, paroxetine) and the SNRI venlafaxine have no deleterious effects on driving ability. Acute use of mirtazapine does produce impairments that diminish to some degree when given as a nocturnal dose and cannot be seen after repeated dosing in healthy controls. Patients obviously benefit from treatment with newer antidepressants; however, at least a subgroup does not reach performance level of healthy subjects. More patient studies are needed that elaborate specific relationships between clinical subtypes of the illness and response to different antidepressants, considering course and duration of illness, co-morbidities and not least neuropsychological and neurobiological characteristics.