Marine predators attract significant attention in ocean conservation planning and are therefore often used politically to promote reserve designation. We discuss whether their ecology and life history can help provide a rigorous ecological foundation for marine reserve design. In general, we find that reserves can benefit marine megafauna, and that megafauna can help establish target areas and boundaries for ecosystem reserves. However, the spatial nature of the interplay between potential threats and predator life histories requires careful consideration for the establishment of effective reserves. Modeling tools such as demographic sensitivity analysis will aid in establishing protection for different life stages and distributional ranges. The need for pelagic marine reserves is becoming increasingly apparent, and it is in this venue that marine predators may be most effectively used as indicator species of underlying prey distribution and ecosystem processes.