Selective serotonin reuptake inhibitors (SSRIs) are a class of drug widely used for treatment of mood disorders, including depression and cardiovascular disease. A search for related articles in the PubMed database was attempted. It covered studies, reports, reviews and editorials of the last 5 years. Pro-inflammatory cytokines, such as TNF-α, IL-1 and IL-6, stimulate central serotonin (5-HT) neurotransmission and are over-expressed in depression, which has been linked with hypothalamic-pituitary-adrenal axis (HPA) hyperactivity. They have also been implicated in the pathogenesis and progression of other stress-induced disorders, like myocardial infarction (MI) and coronary heart disease (CHD), as they seem to modulate cardiovascular function by a variety of mechanisms. Biological mechanisms like these may explain the link between depression and CHD. There are a variety of environmental factors as well as genetic factors that might influence the pharmacogenetics of antidepressant drugs. New generation selective serotonin reuptake inhibitor antidepressants (SSRIs) causing a reduced cardiovascular morbidity and mortality may be related to serotonin platelet abnormalities in depressed patients that are effectively treated by SSRIs. SSRIs such as fluoxetine, paroxetine, sertraline and citalopram are not only considered to be free from the cardiotoxicity of their predecessors but also to function as safe and efficacious agents against depression, platelet activation, atherosclerosis and development and prognosis of coronary heart disease. However, there is a need for more studies in order to establish the exact biochemical mechanisms that are responsible for these diseases and the immunoregulatory effects of chronic use of SSRI medications.