The need for high-k gate dielectrics and metal gates into advanced integrated circuits has re-opened the door to germanium and III-V compounds as potential replacements for silicon channels, offering the possibility to further increase the performances of metal-oxide-semiconductor devices, as well as adding new circuit functionalities. A fundamental issue related to high-mobility channels is the passivation of their interfaces, i.e. achieving a low density of interface defects, approaching state of the art Si-based devices. Promising approaches for the passivation of Ge channels are discussed and insights obtained by combining experimental characterization techniques with first-principles simulations are highlighted.