Water serves as an indispensable part of human life and production. On account of the overexploitation of traditional water sources, the demand for wastewater recycling is expanding rapidly. As a promising water treatment process, membrane distillation (MD) has been utilized in various wastewater treatments, such as desalination brine, textile wastewater, radioactive wastewater, and oily wastewater. This review summarized the investigation work applying MD in wastewater treatment, and the performance was comprehensively introduced. Moreover, the obstructions of industrialization, such as membrane fouling, membrane wetting, and high energy consumption, were discussed with the practical investigation. To cope with these problems, various strategies have been adopted to enhance MD performance, including coupling membrane processes and developing membranes with specific surface characteristics. In addition, the significance of nutrient recovery and waste heat utilization was indicated.