Hox genes encode conserved transcription factors expressed along the antero-posterior axis of vertebrates and invertebrates. In both phyla, HOX proteins control the formation of specific structures in the segments where they are expressed. Because of the global effect they have on segment morphology, the Hox genes are said to control segment identity. Here we review the data available on how HOX proteins regulate their downstream targets and how they mediate the formation of segment-specific structures. Within the segment, the information provided by HOX proteins, tissue-specific transcription factors, and signaling pathway effectors becomes integrated at the enhancer of the target genes, resulting in their localized activation. In general, HOX proteins regulate the morphogenesis of specific organs indirectly by activating networks of transcription factors and signaling molecules, but they can also directly regulate the so-called realizator genes: genes that control the cell behaviors that induce morphogenesis. Here we review some of the Hox-activated networks, the most interesting realizator genes known to date, and summarize how organogenesis is affected in Hox mutants. These examples reveal that only a fraction of the transformations caused by Hox mutations are in fact homeotic (leading to the morphological transformation of a structure present in one segment into that present in another segment). In the cases where Hox gene mutants do not cause homeotic transformations, the wild-type function of the Hox gene is to activate specific cell behaviors (cell proliferation, survival, shape changes, and rearrangements) that lead to the morphogenesis of particular organs. This second non-homeotic function is common to vertebrates and invertebrates, and we argue that it may actually constitute the original HOX function.