The predominance of sour orange rootstock for citrus in the Mediterranean area is currently threatened by the spread of citrus tristeza virus (CTV). As a result, the search for alternative rootstocks resistant to CTV and able to withstand other constraints, such as drought, alkalinity, salinity, Phytophthora and nematode problems, is now considered an urgent priority. Progress in genetic improvement of citrus rootstock by conventional sexual breeding is difficult, mainly because of the reproductive biology and heterozygosity of genitors. These induce important segregations of characters in progeny and a low probability of obtaining recombinant hybrids that combine all the desirable genes and traits of the two parents. In this context, the creation of somatic hybrids is very promising. Indeed, it allows for the accumulation of all the dominant genes of both parents for tolerance to biotic and abiotic factors, irrespective of their level of heterozygosity. This strategy has now been mastered by CIRAD in France with a view to launching a Mediterranean citrus rootstock challenge. Protoplast electrofusions were used for 11 interspecific and intergeneric combinations. Regenerated embryos and plants are studied by flow cytometry and molecular markers in order to select allotetraploid hybrids. 'Me somatic hybrids then undergo an accelerated propagation step, which uses softwood cuttings for further multilocal evaluation of tolerance to biotic and abiotic factors and agronomic rootstock trials.