Through recent advancements in tissue-typing techniques, the true extent of HLA polymorphism has become evident. This has allowed a better assessment of the degree of matching of donor and recipient, which has reiterated the pivotal importance of HLA compatibility for the outcome of a stem cell transplantation. Now that most tissue typing laboratories are technically able to provide a flawless, high-resolution HLA typing, the challenge of the future will be to develop tissue typing-based search strategies that give an optimal chance to find the best donor within the time limits set by the disease of the patient.