Hydrophobic　membranes　used　in　membrane　distillation　(MD)　systems　are　often　subject　to　wetting　during　long-term　operation.　Thus,　it　is　of　great　importance　to　fully　understand　factors　that　influence　the　wettability　of　hydrophobic　membranes　and　their　impact　on　the　overall　separation　efficiency　that　can　be　achieved　in　MD　systems.　This　Critical　Review　summarizes　both　fundamental　and　applied　aspects　of　membrane　wetting　with　particular　emphasis　on　interfacial　interaction　between　the　membrane　and　solutes　in　the　feed　solution.　First,　the　theoretical　background　of　surface　wetting,　including　the　relationship　between　wettability　and　interfacial　interaction,　definition　and　measurement　of　contact　angle,　surface　tension,　surface　free　energy,　adhesion　force,　and　liquid　entry　pressure,　is　described.　Second,　the　nature　of　wettability,　membrane　wetting　mechanisms,　influence　of　membrane　properties,　feed　characteristics　and　operating　conditions　on　membrane　wetting,　and　evolution　of　membrane　wetting　are　reviewed　in　the　context　of　an　MD　process.　Third,　specific　membrane　features　that　increase　resistance　to　wetting　(e.g.,　superhydrophobic,　omniphobic,　and　Janus　membranes)　are　discussed　briefly　followed　by　the　comparison　of　various　cleaning　approaches　to　restore　membrane　hydrophobicity.　Finally,　challenges　with　the　prevention　of　membrane　wetting　are　summarized,　and　future　work　is　proposed　to　improve　the　use　of　MD　technology　in　a　variety　of　applications.