The mammalian brain and central nervous system are especially dependent on the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA) for normative signaling and function, and research suggests that n-3 fatty acid deficiencies are one contributing factor in the increasing prevalence of depressive disorders. However, the reasons for which n-3 fatty acids and mood are connected remain unknown. Atrophy in the hippocampus is one of the most significant neuroanatomical findings in depressed patients, and current therapies for depression tend to increase hippocampal neurogenesis. We recently discovered that the fat-1 transgenic mouse, which has enriched levels of DHA in the brain because it can convert n-6 to n-3 fatty acids, exhibits increased hippocampal neurogenesis. This finding suggests a mechanism by which omega-3 could influence depression and mood; here we expand on the argument that n-3 fatty acids, and DHA in particular, may help prevent and treat depression by virtue of their effects on neurogenesis in the hippocampus. Because DHA can be obtained through the diet, increasing DHA intake in depressed patients or those at risk for depression may be one way of managing the disease and perhaps providing aid to those who have not been able to achieve remission via pharmacological means.