Depression is characterised by depressed mood or/and the loss of interest or pleasure in nearly all activities for a substantial period of time, causing significant distress. Depression is a potentially life-threatening disease. It is a major risk factor for suicide as well as coronary artery disease (CAD) and sudden cardiac death (SCD). It also may be associated with impaired endothelial dysfunction and decreased heart rate variability (HRV). Both conditions seem to persist in patients with depression despite successful antidepressant treatment. During the last few years epidemiological studies as well as clinical trials have suggested a significant role of omega-3 fatty acids in the pathogenesis of depression. As omega-3 fatty acids have been demonstrated to also beneficially influence many of the conditions depression is a risk factor for (CAD, SCD) or may be associated with (decreased HRV, endothelial dysfunction), they may well represent a major advance in the treatment of depression. However more large randomized clinical trials are clearly needed to substantiate that claim.