The fouling behavior of carbon nanotube (CNT) membranes is investigated for large protein biomolecules and a wide variety of small molecules. The CNT membranes are largely fouling resistant, even to untreated river water, due to size exclusion and an inert graphitic core that supports fast fluid flow. However, it is found that bovine serum albumin (BSA) and naphthalene significantly foul membranes due to solution coagulation and π–π stacking, respectively. Small single-walled (SW) CNTs (<1.5 nm i.d.) are difficult to foul with BSA when precipitation is prevented, showing that size exclusion at SWCNT tips can prevent fouling. Electrochemical oxidation, bubble generation and ionic pumping are shown to recover membrane performance. Electrochemical oxidation at greater than +1.4 V is seen to oxidize CNTs as well as biofoulants, but H2 bubble generation at –2 V lifts foulants without damage to the membrane allowing for repeated cycles. Ionic pumping using large cations is seen to remove small molecule foulants adsorbed to the CNT core. The relatively narrow class of foulants and three complementary methods of membrane defouling make the CNT membrane platform a potentially robust system for a wide variety of chemical separations and environmental water treatments.