Nanofiltration (NF) technology offers several advantages over classic separation processes. NF membranes have been increasingly implemented in water treatment processes (e.g., desalination of brackish water and seawater) and for wastewater (e.g., textile, pulp and paper, pharmaceutical, and agro-industrial). The specific selectivity toward small solutes and the lower energy consumption of NF membranes have enhanced their use. However, some drawbacks need to be faced when NF is applied on an industrial scale. The main drawback is fouling that reduces the production capacity of the plant and shortens the membrane service lifetime if of irreversible nature, thus increasing the operating and capital costs. Moreover, fouling alters the selectivity of the membrane and thus the rejection efficiency. This chapter focuses the use of NF for the treatment of different agro-industrial effluents (such as dairy, tomato, and olive oil) and addresses membrane fouling as the main drawback against NF competitiveness.