Because of the high demand of organs, the usage of marginal grafts has increased. These marginal organs have a higher risk of developing ischemia-reperfusion injury, which can lead to posttransplant complications. Ex situ machine perfusion (MP), compared with the traditional static cold storage, may better protect these organs from ischemia-reperfusion injury. In addition, MP can also act as a platform for dynamic administration of pharmacological agents or gene therapy to further improve transplant outcomes. Numerous therapeutic agents have been studied under both hypothermic (1–8°C) and normothermic settings. Here, we review all the therapeutics used during MP in different organ systems (lung, liver, kidney, heart). The major categories of therapeutic agents include vasodilators, mesenchymal stem cells, antiinflammatory agents, antiinfection agents, siRNA, and defatting agents. Numerous animal and clinical studies have examined MP therapeutic agents, some of which have even led to the successful reconditioning of discarded grafts. More clinical studies, especially randomized controlled trials, will need to be conducted in the future to solidify these promising results and to define the role of MP therapeutic agents in solid organ transplantation.