Membrane distillation (MD) is an emerging thermally-driven technology that poses a lot of promise in desalination, and water and wastewater treatment. Developments in membrane design and the use of alternative energy sources have provided much improvement in the viability of MD for different applications. However, fouling of membranes is still one of the major issues that hounds the long-term stability performance of MD. Membrane fouling is the accumulation of unwanted materials on the surface or inside the pores of a membrane that results to a detrimental effect on the overall performance of MD. If not addressed appropriately, it could lead to membrane damage, early membrane replacement or even shutdown of operation. Similar with other membrane separation processes, fouling of MD is still an unresolved problem. Due to differences in membrane structure and design, and operational conditions, the fouling formation mechanism in MD may be different from those of pressure-driven membrane processes. In order to properly address the problem of fouling, there is a need to understand the fouling formation and mechanism happening specifically for MD. This review details the different foulants and fouling mechanisms in the MD process, their possible mitigation and control techniques, and characterization strategies that can be of help in understanding and minimizing the fouling problem.