While the focus of the work around the Smart Grid concept is mostly on electricity networks, there is a huge potential to increase the energy system environmental and economic efficiency by optimizing the interactions with other energy vectors and networks at both operational and planning stages. This naturally leads to the extended concept of Smart Multi-Energy Grid. The main aim of this talk is thus to present a number of interactions between electricity, heat, gas, hydrogen, transport sector, and so on, and to highlight the opportunities from unlocking the efficiency and flexibility potential that lies in other sectors that electricity interacts or might/will interact with. Technical, commercial, and regulatory challenges, benefits, and opportunities for different actors and at different levels of the energy chain of the Smart Multi-Energy Grid will then be discussed and exemplified. Particular stress will be put on the potential for developing and fast-growing Countries to look into this innovative framework.