It is well known that the optimum proton-exchange membrane material for a direct methanol fuel cell (DMFC) should have a high proton conductivity and low methanol crossover. Such a combination of properties is difficult to achieve and, in general, membranes with low methanol permeability also exhibit sluggish proton conduction. Consequently, a major objective of DMFC membrane development has been to maximize the conductance/permeability ratio. Alternatively, attempts have been made to optimize both the MEA (membrane-electrode-assembly, composed of the membrane and attached catalyst layers) structure and the operational conditions of a DMFC in order to effectively utilize existing membrane materials. Some investigators employ thin membranes to decrease the ohmic resistance of an MEA and dilute methanol feed concentrations to lower methanol crossover. Membrane thickness, in particular, has a direct bearing on the primary processes that cause DMFC power losses, via ohmic losses (IR drop) and methanol crossover flux (which causes cathode depolarization and poisoning of the cathode catalyst by CO, a product of methanol oxidation). It is, therefore, of prime importance to understand the interdependence of membrane thickness and DMFC operating conditions (e.g., methanol feed concentration, temperature and air/oxygen flow rate and pressure) on the short-term and long-term performance of a direct methanol fuel cell.  In the present talk, the effects of membrane thickness on the initial and long-term power output from a DMFC will be presented (here, long-term is defined as a few days of fuel cell operation). DMFC performance plots (voltage vs. current density) will be described/discussed for different proton-exchange membranes (Nafion, sulfonated PEEK, and sulfonated polyphosphazene) of varying thickness. In general, we have found that the power generated using thin a membrane is initially high (due to lower resistive losses) but falls rapidly (within a few hours) due to poisoning of the cathode by CO, whereas the initial performance with a thicker membrane is low (due to its high resistance) but is more stable during long-term operation because there is less CO poisoning of the cathode (due to lower methanol crossover).