Membranes, as the primary tool in membrane separation techniques, tend to suffer external deposition of pollutants and microorganisms depending on the nature of the treating solutions. Such issues are well recognized as biofouling and is identified as the major drawback of pressure-driven membrane processes due to the influence of the separation performance of such membrane-based technologies. Herein, the aim of this review paper is to elucidate and discuss new insights on the ongoing development works at facing the biofouling phenomenon in membranes. This paper also provides an overview of the main strategies proposed by “membranologists” to improve the fouling resistance in membranes. Special attention has been paid to the fundamentals on membrane fouling as well as the relevant results in the framework of mitigating the issue. By analyzing the literature data and state-of-the-art, the concluding remarks and future trends in the field are given as well.