In December 2003, Giot et al. (1) published a systematic investigation of the protein interaction network—the interactome—of Drosophila melanogaster. Giot et al. produced a draft map of 7,048 proteins and 20,405 interactions, which they then refined to “a higher confidence map of 4,679 proteins and 4,780 interactions.” The magnitude of the undertaking led to the study being lauded as the “dawn of systems biology” in a number of commentaries and news releases. Giot et al.'s study was preceded and followed by a number of investigations of the interactomes of other species, ranging from bacteria to humans (2–5). However, none of these studies was able to provide an estimate of the actual size of the interactome being sampled. In a systematic statistical study published in this issue of PNAS, Stumpf et al. (6) provide convincing estimates of the interactome size of four organisms, including humans.