DNA sequence taken in isolation from a single organism reveals very little about gene function. In recent years, comparative genomics has provided new insights into our understanding of gene function and the evolutionary relationships that exist between genes. In functional genomics, computational analyses have been particularly useful in deducing putative functions for genes that can be tested by experimental analysis “wet” biology. Until recently, such methods for predicting function relied heavily on sequence comparison. On page 609, Galperin and Koonin discuss several newly developed computational approaches that significantly extend the predictive power of comparative genomics beyond sequence comparison. By analyzing the evolutionary relationships between protein families, protein and domain fusion comparisons in different species, gene adjacency in different genomes, and gene expression patterns, they argue computational genomics will provide deeper insights into functional interactions between proteins and information about specific functions.