An uncertainty heretofore has existed over the importance of Antarctic toothfish (Dissostichus mawsoni) as prey of top predators in the Ross Sea. We reviewed the literature to assess the relative weight that should be given to direct, observational evidence of predator diet composition, as opposed to indirect evidence from scat and biochemical analysis. As a result of this assessment, it is evident that toothfish are an important prey of Weddell seals (Leptonychotes weddellii). Recent findings show the seals do not eat toothfish hard parts, thus providing the reason that toothfish have seldom been detected in scat or stomach samples; biochemical samples have been taken only from seal populations where toothfish do not occur. On the basis of data from an under ice observation platform, non-breeding seals in McMurdo Sound take 0.8-1.3 toothfish per day. Seals with video recording equipment were seen to closely encounter toothfish but for unknown reasons did not often pursue for capture. It is estimated that the non-breeding portion of the seal population in McMurdo Sound, during spring and summer, consume about 52 tonnes of toothfish. Too many unknowns exist to estimate what the larger, breeding portion consumes during that and other parts of the year, although it should not be trivial. Much less is known quantitatively about the importance of toothfish to type-C (fish-eating) killer whales (Orcinus orca), but observational evidence indicates toothfish consumption to be common. A decline in the abundance of toothfish in McMurdo Sound appears already to be leading to a decline in the number of foraging killer whales. Care must be taken in managing the Ross Sea toothfish fishery, as the potential is great that, given the high degree of trophic overlap and competition among top predators, likely cascades will lead to dramatic changes in the populations of charismatic megafauna, particularly the seals, should the toothfish, probably the most important predator of fish in the system, become overly depressed.