Stress-related mood deterioration and affective disorders, such as depression, are among the leading causes of disease burden throughout the world, and are associated with severe medical consequences and mortality. Research has shown the involvement of dysfunctional brain serotonin (5-HT) biochemistry as a vulnerable biological factor in the onset of mood disturbances. Since the production of brain serotonin is limited by the availability of its plasma dietary amino acid precursor tryptophan, different foods and dietary amino acids that influence tryptophan availability are thought to alter affective behavior by changing brain 5-HT synthesis. Most dietary manipulation studies, however, reveal only modest affective changes, and note that these particularly occur in stress-prone or affected (sub-clinical) subjects. The current paper briefly summarizes evidence for the involvement of diminished brain serotonin function in affective disorders, discusses how this can be assessed and influenced by dietary manipulation procedures, and also notes how beneficial effects of dietary brain serotonin manipulation on affective behavior may be mediated by stress-induced brain serotonin vulnerability.