The almost ubiquitous, though undesired, deposition and accumulation of suspended/dissolved matter on solid surfaces, known as fouling, represents a crucial issue strongly affecting the efficiency and sustainability of micro-scale reactors. Fouling becomes even more detrimental for all the applications that require the use of membrane separation units. As a matter of fact, membrane technology is a key route towards process intensification, having the potential to replace conventional separation procedures, with significant energy savings and reduced environmental impact, in a broad range of applications, from water purification to food and pharmaceutical industries. Despite all the research efforts so far, fouling still represents an unsolved problem. The complex interplay of physical and chemical mechanisms governing its evolution is indeed yet to be fully unraveled and the role played by foulants’ properties or operating conditions is an area of active research where microfluidics can play a fundamental role. The aim of this review is to explore fouling through microfluidic systems, assessing the fundamental interactions involved and how microfluidics enables the comprehension of the mechanisms characterizing the process. The main mathematical models describing the fouling stages will also be reviewed and their limitations discussed. Finally, the principal dynamic investigation techniques in which microfluidics represents a key tool will be discussed, analyzing their employment to study fouling.