The use of unrelated donors for bone marrow transplantation (BMT) is associated with an increased morbidity and mortality when compared with HLA-identical donors, primarily due to an increased rate of graft-versus-host disease, but also to increased susceptibility to infections and graft failure. HLA matching for donors and recipients is the single most important factor influencing the outcome of BMT. However, unrelated donor selection generally relies on matching only for HLA-A, -B and -DR antigens without considering potential incompatibility for other HLA loci, such as HLA-C, -DQ and -DP. In addition, other factors that affect the outcome of BMT need to be taken into consideration in selecting the best unrelated donor. In this review, we will focus on the effects of HLA-associated factors in determining the result of a transplant procedure. We will also mention other relevant factors, drawing on our experience of laboratory studies performed at The Anthony Nolan Research Institute and clinical studies at the Hammersmith Hospital in London.