After 25 years of research on EMDR therapy’s mechanisms, we cannot provide an evidence based explanation for all its treatment effects. Before examining mechanisms, we must first consider differences between mediators, mechanisms and moderators of change in general psychotherapy (Kazdin, 2007) and in EMDR therapy. An analysis of the literature generates six distinct hypothesized mechanisms of action that provide diverse multiplex effects, sometimes converging and sometimes diverging, leading to various outcomes in different clinical contexts and in different EMDR procedures. Implications for EMDR therapy include moderators such as degree of structural dissociation and mediators including modes of bilateral stimulation.