Formation of nitrogen fixing symbioses between Rhizobium and legumes requires the co-ordinated expression of many bacterial and plant genes. Exchange of a series of molecular signals between the symbionts modulates transcription of nodulation and nitrogen fixation loci. Signal exchange also permits the selection of compatible partners from the many bacteria found in the rhizosphere of potential hosts. Amongst the signals exchanged, flavonoids released by host-plants act in conjunction with bacterial NodD transcriptional regulators to activate transcription of rhizobial nodulation genes. In turn, the micro-symbionts secrete families of lipo-chitooligosaccharide molecules called Nod-factors which induce formation of root nodules as well as permit entry of rhizobia into root-hairs. Once the bacteria are within the plant, expression of nitrogen fixation genes is partly controlled by low levels of free oxygen. Other signals have been recently discovered that also control the development of symbiotic interactions. Mostly because of an extremely broad host-range, Rhizobium sp. NGR234 is an ideal candidate to study these supplementary keys to the legume doors. Genetic analysis of the 536 kb symbiotic plasmid of NGR234 revealed a functional type three secretion system (TTSS) responsible for the flavonoid-dependent secretion of a number of proteins. Disruption of the TTSS machinery or the genes coding for the secreted proteins modifies the symbiotic properties of the NGR234 mutants.