Overview of the existing theories regarding pathomechanism in Gorham-Stout syndrome. Broken lines and grey arrows show theoretical considerations still lacking proof. Role of trauma still remains uncertain. Elevated levels of Il-6 and differentiation factors Il-1β and RANKL may stimulate osteoclasts and lead to bone resorption while PDGF-BB, IL-8, and VEGF-A may activate endothelial cells and others via CD105 and TGF-beta1-receptor. This may result in vascular malformation and lymphangiomatosis. Both are characteristics of Gorham-Stout syndrome.