Fragile X syndrome is now a well established common clinical entity and most of those who are aware of the condition probably know that it takes its name from a rare fragile site (FRAXA) on the X chromosome. This is the best known fragile site and its clinical significance is clear. Similar, but a little less known is FRAXE, a fragile site close to that associated with fragile X syndrome, but in this case associated with a mild form of non-specific X-linked mental retardation. These are the only two fragile sites that are unequivocally of clinical significance. A fragile site within the CBL2 oncogene on chromosome 11 has been mapped very close to the deletion breakpoint in a handful of patients with Jacobsen syndrome. It is doubtful that parents with FRA11B are at increased risk of having children with Jacobsen syndrome, but this cannot be ruled out. The common fragile sites have been implicated in oncogenesis since shortly after their discovery in the early 1980s. While a couple of these are within genes that have been implicated in cancer it is unclear whether either the fragile sites, or the genes in which they are located are important in cancer. It may be that the common fragile sites are regions of genomic instability and that this instability is increased in malignant cells, analogous to the enhanced instability seen at microsatellite loci in a number of tumours. Since we all have the common fragile sites there is no suggestion that they give anyone an increased risk of developing malignant disease. In dealing with patients who are found to have fragile sites, other than FRAXA, FRAXE and possibly FRA11B, considerable reassurance can be given that they are not at increased risk of having children with congenital disease or developing disease themselves because of their fragile sites.