An analysis of NMDP data shows that allele-level matching for HLA A, B, C, and DRB1 is preferred in the selection of adult unrelated donors. If mismatching is unavoidable, mismatches at HLA B or C may be better tolerated than those at A or DRB1. Whether mismatches are at the allele level (ie, within an antigen group) or at the antigen level makes no difference in outcome, except at HLA C where allele mismatches are better tolerated. Matching for HLA DQ and DP should be prioritized below matching at the 4 major loci. These findings are compared and contrasted with previous publications. The impact of HLA matching on major outcomes in umbilical cord blood (UCB) transplantation continues to be refined. Total nucleated cell dose was previously thought to be sole determinant of outcome with partially HLA matched UCB transplantation, but HLA matching, particularly at low total nucleated cell dose, appears to play an important role. Relatively small sample sizes limit the consistency of findings from cord blood studies, but the consensus supports consideration of both total nucleated cell dose and HLA matching in the selection of optimal UCB units. As search considerations for both adult donors and umbilical cord blood units have become more complex, the National Marrow Donor Program has developed software, services and relationships to ease the burden on transplant teams.