Nafion, a perfluorosulfonic acid proton exchange membrane (PEM), has been widely used in direct methanol fuel cells (DMFCs) to serve as a proton carrier, methanol barrier, and separator for the anode and cathode. A significant drawback of Nafion in DMFC applications is the high anode-to-cathode methanol fuel permeability that results in over 40% fuel waste. Therefore, the development of a new membrane with lower permeability while retaining the high proton conductivity and other inherent properties of Nafion is greatly desired. In light of these considerations, this paper discusses the research findings on developing Nafion-based membranes for DMFC. Several aspects of the DMFC membrane are also presented, including functional requirements, transport mechanisms, and preparation strategies. More importantly, the effect of the various modification approaches on the performance of the Nafion membrane is highlighted. These include the incorporation of inorganic fillers, carbon nanomaterials, ionic liquids, polymers, or other techniques. The feasibility of these membranes for DMFC applications is discussed critically in terms of transport phenomena-related characteristics such as proton conductivity and methanol permeability. Moreover, the current challenges and future prospects of Nafion-based membranes for DMFC are presented. This paper will serve as a resource for the DMFC research community, with the goal of improving the cost-effectiveness and performance of DMFC membranes.