Recent registry studies have established umbilical cord blood (UCB) transplantation as a safe and feasible alternative to bone marrow transplantation in adults when no sibling donor is available. There is, however, no gold standard to guide optimal treatment choices. We review here factors leading to the choice of the 'best available donor' and 'best available unit' in the case of UCB. For instance, it is clear that higher cell dose may partially overcome the negative impact of certain histocompatibility leukocyte antigen (HLA) disparities in UCB transplantation, leading us to choose the more closely HLA-matched unit with a cell dose >2.5 x 10(7)/kg. New approaches in adult UCB transplantation are systematically covered, with a quantitative appreciation of the evidence available to date. Reduced intensity conditioning, for example, broadens the range of potential recipients by reducing transplant-related mortality, but suffers from unproven risks and benefits long term. Potential advantages of multiple units over single unit transplants are discussed, with a particular emphasis on confounding factors that impact interpretation. The limited clinical results of ex vivo UCB expansion, the possible benefits of co-infusion of haploidentical cells and controversial issues (e.g. killer immunoglobulin-like receptor matching and alternative graft sources) are also addressed with a debate on the future of UCB transplantation.