Depression is a mental disorder that is likely to affect daily functions, including driving ability. However, driving performance of depressed patients remains poorly investigated. We will present 2 studies designed to assess driving performance of patients receiving long-term antidepressant treatment. The first study compared driving performance of untreated depressed patients, depressed patients receiving SSRI or SNRI treatment for 6–52 weeks and matched healthy controls. The second study compared driving performance of long-term users of sedative antidepressants to that of matched healthy controls. A standardized on-the-road driving test was used to assess standard deviation of lateral position (SDLP), a measure of weaving. In the first study, mean SDLP of untreated and treated patients were significantly higher as compared to SDLP of matched controls. Driving impairment in the treated group was significantly less as compared to the untreated group. SDLP was positively correlated to severity of depression across both groups of patients. In the second study, SDLP of patients receiving sedative antidepressants (e.g. mirtazapine) during 0,5–3 yrs was significantly higher as compared to matched controls. Driving performance of patients receiving sedative antidepressants for more than 3 yrs did not differ from matched controls. Severity of depression in these patients groups was low. It is concluded that symptoms of depression are a major cause of driving impairment. Reductions in severity of depression through antidepressant treatment reduce severity of driving impairment. Sedative antidepressants such as mirtazapine however can still induce driving impairment in patients with remission for up to 3 yrs of use.