Prospective clinical trials for blood transplantation and BMT are made more difficult by limited patient numbers, heterogeneity of clinical management strategies, and high-intensity therapy with frequent and toxic competing hazards. To address the challenges of prospective clinical study of BMT, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN), sponsored by the National Heart, Lung, and Blood Institute/National Cancer Institute, was established. The network's charge is to design and execute multicenter clinical trials requiring participation from the network and from noncore centers for successful performance and to address rare diseases and unique populations that could not be well studied in individual centers. The BMT CTN organizational structure, current portfolio of studies, and scientific agenda are reviewed. Opportunities for investigators in any institution to propose trials and participate are outlined.