Despite all promising perspectives and new research in nanofiltration, for example, in drinking water production, in wastewater treatment, the food industry, the chemical and pharmaceutical industry, and many other industries, there are still some obstacles that slow down large-scale applications. Fouling is an irreversible and time-dependent phenomenon, and it is related to the characteristics of the membrane and solute-solute and solute-membrane interactions. Therefore, an understanding of fouling mechanisms such as fouling characteristics and consequences, fouling mathematical models, and physicalchemical and processing factors affecting fouling, are very important. As a result, the aim of this chapter is to present some phenomena that contribute to fouling: physicalchemical interactions, pore mechanical blocks, and deposit of suspension material on membrane surface.