Cadaveric donors are often presented with several pathophysiological alterations in hemodynamics, hormone balance, body temperature, and lung function. Therefore, appropriate medical management of a potential organ donor can be very challenging. However, it is one of the main conditions that ensures the preservation and quality of organs. There are still many controversies and conflicting recommendations in the management of organ donors. In this chapter, we present the main factors that influence early graft survival and transplant outcome, including socioeconomic and organizational factors, factors related to the demographics and genetics of the donor, and factors related to the direct donor preparation until the explantation procedure. The aim of this chapter is to cover all controversies and to abolish uncertainties in order to facilitate the management of potential donors.