A lipochitosaccharide-based signal molecule that is secreted by Rhizobium, named Nod factor (NF), induces root nodule formation in legumes. This molecule is also essential for the establishment of bacterial infection. Genetic analyses in the legume species Lotus japonicus and Medicago truncatula have led to the identification of many components of the NF signaling cascade. At least three of these genes do not function exclusively in the Rhizobium symbiosis but are also essential for the formation of mycorrhiza, an endosymbiosis found in many higher plant species. Recent studies have advanced our understanding of the functions of NF signaling genes in the Rhizobium infection process and the extent to which these genes are unique to legumes.