Plants form diverse symbioses with nitrogen-fixing bacteria to gain access to ammonium, a product of the prokaryote-exclusive enzyme nitrogenase. Improving the symbiotic effectiveness of crop plants like maize, wheat or rice is a highly topical challenge and could help reduce the need for energy-intense nitrogen fertilizer in staple food production. Root nodule symbiosis (RNS) constitutes one of the most productive nitrogen-fixing systems, but it is restricted to a small group of related angiosperms. Here, we review the genetic regulation of RNS and its interconnections with other plant symbiosis or plant developmental programs. Since RNS uses genetic programs that are widely conserved in land plants, we evaluate the prospects for a transfer to plants that are currently non-nodulating.