Recent technological developments have made possible the application of telemedicine in the management of trauma and emergency situations, especially in remote areas and isolated communities. What has not been tested effectively remains the use of telemedicine in major disaster management, despite a few examples previously reported. The biggest promise of telemedicine for disaster management is the intervention in the ‘golden hour’, which is the 60 minutes immediately following a traumatic event. While transformation of a chaotic situation caused by a disaster through the use of telemedicine has been demonstrated, the use of a multinational telemedicine system (MnTS) in the management of these situations has not been fully demonstrated. Furthermore, what is truly attractive is the use of the multinational telemedicine concept as an intervention method in major disasters and catastrophes across the different countries or regions, where a number of elements are tested, including language, expertise, communication, licensure and other components. While there are a number of challenges in the application of the MnTS, the opportunities and potential benefits outweigh these challenges. In this chapter, we review both challenges and opportunities in application of telemedicine in the disaster management. Establishing a nationwide program of telemedicine in one country is complex and has its own challenges. Efforts in Albania, Kosova, and Cabo Verde serve as examples to illustrate these challenges using established telemedicine programs to manage disasters in a structured pre-planned way, provides a foundational process. Aside from a few demonstrations over the past several decades, there is limited data on how existing systems are applied. Telemedicine efforts in Albania have been utilized at a high level for administrative management of flooding in 2010. There are a number of challenges in developing and deploying a MnTS to a country or region affected by disasters. These will be reviewed in this chapter.