Arterial and venous thromboembolism are common causes of morbidity and mortality in the Western world. Mental disorders are also highly prevalent with a lifetime risk of experiencing any psychiatric disease ranging between 32 % and 37 %. Depression and schizophrenia may increase the risk of thromboembolism through genetic, behavioral, and biological mechanisms. Treatment of psychiatric patients with psychotropic drugs is imperative to improve quality of life and to reduce morbidity and mortality. However, studies have shown that psychotropic drugs themselves may modify the risk of arterial and venous thromboembolism, which should be taken into consideration when using these drugs in clinical practice. This association is, however, multifactorial, complex and susceptible to several confounding factors. Psychotropic drugs are widely prescribed, also among patients with cardiovascular disease. Therefore, understanding the association with thromboembolism and the underlying pathophysiological mechanisms is of major importance and will be reviewed in this chapter.