The organ shortage is widely acknowledged as the most critical factor hindering the full realization of success for solid organ transplantation. Innovation in the areas of donor management and organ preservation offers the most realistic hope to improve both the quality and size of the current organ supply. Although the basic science dissecting the complex processes of brain death and ischemia/reperfusion injury is replete with exciting discoveries, the clinical science investigating donor management and organ preservation is sparse in contrast. This review will survey the current landscape of trials to mitigate organ injury through interventions administered to donors in vivo or organs ex vivo. Consideration will then be given to the scientific, logistical and ethical obstacles that impede the transformation of laboratory breakthroughs into innovative treatments that simultaneously improve organ quality and supply.