There is increasing evidence that stress and depression may play a crucial role in the aetiology and pathophysiology of fibromyalgia (FM). We first review recent studies on the possible role of life stress, including childhood trauma, in FM. Subsequently we focus on clinical and aetio-pathogenetic links between stress, depression and pain. We put forward the hypothesis that chronic stress/depression may contribute to a dysregulation of neuro-endocrine, immune and central pain mechanisms in FM. Finally, we discuss some future directions, including the use of new conceptual models, research topics and strategies, as well as potential implications from recent studies in affective disorders for the treatment of FM.