Descemet membrane endothelial keratoplasty (DMEK) has become the goldstandard in the treatment of Fuchs endothelial corneal dystrophy and early stages of (pseudophakic) bullous keratopathy due to the safer ´closed globe` surgery, the fast and excellent visual recovery and low complication rates. In those cases, DMEK can often be performed in a standardized manner. Given the outstanding clinical outcomes, the spectrum of indications has expanded in the past years: thus, also more complex cases, such as eyes with advanced corneal edema, altered anterior chamber anatomy, failed lamellar grafts, failed penetrating keratoplasty, as well as, phakic, aphakic and vitrectomized eyes are being treated with DMEK. Although DMEK surgery in complicated eyes proved feasible, the procedure is technically more challenging because of the impaired visualization during surgery and the unpredictable graft behaviour. Surgical strategies to accomplish DMEK in complex eyes have been suggested and customization of recipient/donor characteristics (donor age, graft size) may facilitate the surgery. Still, clinical outcomes appear not as good as in standard indications and there is uncertainty concerning the long-term graft survival.