Depression is a common disease that is often pharmaceutically treated with tricyclic antidepressants (tcas) and selective serotonin reuptake inhibitors (ssris). Both groups of drugs have proven to be effective in treating depressive symptoms, however they differ in adverse effect profile. This chapter discusses their effects on driving ability. On the road driving tests have shown that tcas such as imipramine, doxepine and amitriptilyne significantly impair driving performance after single dose administration. However, after one to two weeks of daily treatment tolerance developed and no significant driving impairment was reported. Sedative antidepressants such as mianserin and mitrazapine administered at bedtime produce significant driving impairment the morning following single dose administration and after one week of daily treatment. In contrast, ssris such as fluoxetine and paroxetine had no significant effects on driving ability. Also, venlafaxine did not affect driving performance. The chapter concludes by discussing that untreated depression impairs driving ability and that reported somnolence correlates significantly with reduced driving performance.keywordssingle dose administrationkdyh ehhqwkdq wkdwthese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.