A striking characteristic of many animal species ranging from worms to humans is their metameric or segmental organization. The striking repetition of anatomical modules along the anteroposterior axis, which characterizes segmentation, has been an intense subject of study since the 19th century when it was first taken by scientists like Geoffroy Saint Hilaire as an argument to support the concept of unity of the body plan among animals. While it remained descriptive for a long time, the segmentation field has witnessed much progress during the past 30 years. Studies of the fly segmentation cascade pioneered by Nusslein-Volhard and Wieschaus during the early 1980s have provided a major paradigm for future developmental genetics and have also led to the elaborate genetic schemes underlying the establishment of this characteristic pattern during fly embryogenesis (Nusslein-Volhard and Wieschaus,1980). During the late 1990s, the discovery of a molecular oscillator—the segmentation clock—and its association with vertebrate somite formation has boosted studies of vertebrate segmentation (Palmeirim et al.,1997). This special issue of Developmental Dynamics, dedicated to segmentation, comprises a series of reviews essentially focusing on the segmentation clock and its regulation. Existence of this oscillator had been predicted on theoretical grounds in the clock and wavefront model proposed during the 1970s (Cooke and Zeeman,1976). Experimental demonstration of the existence of the oscillator provided a striking example of the predictive value of such theoretical models. Few examples of oscillators exist in developmental biology, and the segmentation clock provides a unique model of periodic regulation in patterning. Predicting the behavior of such oscillatory systems is often beyond intuition, and mathematical modeling becomes required (Pourquie and Goldbeter,2003). Several models accounting for different aspects of the clock behavior are discussed in this issue. The molecular mechanisms underlying the oscillations in several vertebrate species are also presented. Whereas several models argue in favor of simple regulatory circuits involving negative autoregulation (and delay) by transcription factors of the hairy and enhancer of split family acting in fish and mouse (Bessho et al.,2003; Lewis,2003; Hirata et al.,2004), recent microarray studies have identified a large network of signaling genes belonging to the Notch, Wnt, and FGF families (Dequeant et al.,2006). Thus, while significant progress has been made, the molecular nature of the clockwork underlying the oscillator remains poorly understood. A major role of the segmentation clock is thought to be the positioning of segmental boundaries. The role of genes of the Mesp2 transcription factor family which respond to the periodic clock signal has recently been shown to be critical for defining the future segment (Morimoto et al.,2005). Mesp2 controls a complex morphogenetic program resulting in boundary formation and specification of anterior and posterior somite compartments, ultimately leading to formation of the morphological segmental units. The clock drives the coordinated periodic expression of cyclic genes in the tissue that will generate the somites, the presomitic mesoderm (PSM). This finding results in the rhythmic production of a transcriptional wave that sweeps along the PSM each time a new somite forms (Palmeirim et al.,1997; Holley et al.,2000; Jiang et al.,2000). A remarkable property of this behavior is the synchrony with which the oscillations occur in nearby cells, resulting in the smooth dynamic pattern observed. Experimental evidence now supports a role for cell–cell communication, and more specifically, the Notch signaling pathway in this synchronization process first postulated in zebrafish (Jiang et al.,2000; Horikawa et al.,2006). The synchronization of the individual oscillators of PSM cells is discussed in several reviews in this issue. Whereas it appears to be a major player in the vertebrate segmentation process, Notch signaling is not involved in fly segmentation. In fact, the molecular mechanisms underlying the fly and the vertebrate segmentation processes appear strikingly different. However, the fly is a highly diverged insect that has lost the progressive mode of axis formation observed in vertebrates and in many segmented invertebrates. Surprisingly, Notch appears to play a role in the segmentation of such invertebrate species as the spider (Stollewerk et al.,2003), and recent data suggest that segmentation might not be as divergent as comparison between the fly segmentation cascade and the segmentation clock might suggest. In humans, severe disruptions of the segmentation pattern of the vertebrae are generally called congenital scoliosis (Erol et al.,2004). Such malformations are thought to arise from defects in embryonic segmentation, and thus far, this idea is supported by the fact that all the genes associated with familial congenital scoliosis are linked to the segmentation clock. Our current knowledge about these genes and their human phenotypes are reviewed in this issue. Furthermore, a novel classification for human vertebral defects established by the Nomenclature Committee of the International Consortium on Vertebral Anomalies and Congenital Scoliosis (ICVAS) is included. This classification will hopefully provide a useful tool to describe human and animal segmentation defects in a comparable manner, allowing comparative studies.