Direct fisheries interactions pose a serious threat to the conservation of many populations and some species of marine mammals. The most acute problem is bycatch, unintended mortality in fishing gear, although this can transition into unregulated harvest under some circumstances. A growing issue in some fisheries is depredation, in which marine mammals remove captured fish from nets or lines. Depredation reduces the value of catch and may lead to a greater risk of entanglement and the potential for retaliatory measures taken by fishermen. The conservation threat caused by direct fisheries interactions is most dire for small populations of cetaceans and dugongs. Immediate action is needed to assess the magnitude of bycatch, particularly in many areas of Africa and Asia where little work has been conducted. New and innovative solutions to this problem are required that take account of the socioeconomic conditions experienced by fishermen and allow for efficient transfer of mitigation technology to fisheries of the developing world.