Graft failure through endothelial cell loss is a constant threat throughout the lifetime of a corneal graft. It can occur at various time points after transplantation. Primary graft failure has nowadays become increasingly rare owing to meticulous eye banking methods and improved surgical techniques. Corneal graft rejection is always held responsible for endothelial cell loss. However a rejection episode that is promptly and adequately treated does not necessarily lead to a higher than expected cell loss. A more smouldering danger to ultimate graft survival is late endothelial failure. This gradual graft decompensation is secondary to a decrease in cell density below that necessary to maintain corneal deturgesence. The process of transplantation itself seems to set off a series of events (possibly immunological) that greatly exacerbates the endothelial cell loss compared to virgin corneas. This accelerated cell loss persists for at least 10-15 years after transplantation, after which a more-stable situation is reached and cell attrition returns to normal rates. This provides a strong rationale for setting high donor standards of minimal cell density. Newer transplantation techniques such as deep anterior lamellar keratoplasty and deep lamellar endothelial keratoplasty could provide possible solutions to prevent this late endothelial failure. However they still have to prove themselves in the long run.