Membrane distillation (MD) is a hybrid thermal-membrane desalination process that can use either low-grade waste heat and/or solar energy with hydrophobic membranes to desalinate high-salinity brines and produce high quality distillate. A research consortium was launched to investigate the application of the MD process, at lab and pilot scale, for desalination of concentrated brines. Bench scale results showed the presence of antiscalants in the concentrated brines minimized the scale precipitation potential and offered stable membrane permeability performance. Various MD technologies were screened, and two suitable technologies were selected for field-testing. Pilot unit A was based on multi-effect vacuum showed a stable flux of 6.2 LMH with excellent salt rejection (> 99.9%) from the concentrated brine discharged from thermal desalination plant in Qatar. That pilot unit was also field tested on hypersaline groundwater in Texas (USA) to generate fresh water for reservoir fracking in unconventional oil production operations. The MD unit was coupled with humidification/dehumidification (HDH) unit to achieve zero liquid discharge (ZLD) for inland applications. The MD unit was operated at 40% recovery producing distillate of < 20 mg/L total dissolved solids (TDS) and observed a stable flux of 5 LMH. Key challenges that are critical for large-scale deployment of MD technology were identified at the end of the field-testing program. Finally, a review of active MD technologies was conducted to highlight recent promising developments for full-scale applications.