Membrane distillation (MD) is a membrane-based thermal distillation process in which a non-wetted microporous membrane is used to provide the pathway for vapor transport while preventing the salty feed solution from mixing with the distillate. It is therefore critical to prevent the pores from blockage, as otherwise water flux will be hindered, or from wetting, as otherwise salt rejection would become unacceptably low. Maintaining the functionality of an MD membrane is thus challenging when the feedwater contains fouling and wetting agents. In this presentation, I will systematically discuss how membranes with special wetting properties can be leveraged to address the challenges of fouling, wetting, and mineral scaling in MD.