The interrelationship of brain and body sizes has been the subject of investigations for over a hundred years. These studies have demonstrated that variation in brain weights is much smaller than that in body weights; consequently, scaling studies are ones of negative allometry. Furthermore, the variability in brain weight is greater when comparisons are between species rather than among individuals of the same species, and the degree of variability in brain size differs among orders. The largest shifts in brain sizes relative to changes in body weights are found when comparing different ontogenetic stages. Debate continues as to the importance of metabolism in determining the interrelationship of brain-body weights for interpreting differences in relative brain size. Although past advances in the study of brain-body size associations have come by increasing the size of the data bases and by improved statistical analyses, the recent utilization of transgenic animals may provide new insights into the mechanism of this association.