Developing herbicide resistance in forsaken small crops could be a way to maintain food and cultivation system diversity, otherwise they would disappear due to the impossibility or cost to control the weeds. It is the case with foxtail millet, Setaria italica, a small grain, preferentially autogamous, C4 cereal. Three different herbicide-resistant materials were developed using wild germplasm resources. They allowed: 1) to better characterize the resistance mechanisms and inheritance; 2) provide plant materials to test the efficiency of the crop resistance at field level; and 3) experiment on the possible flow back of the resistance gene to the wild relative and among varieties. 1) The heredity of the resistance was maternal, nuclear recessive and nuclear dominant for resistance to atrazine, trifluraline and sethoxydim, respectively. In the three cases the resistance was due to a single nucleotide mutation: psbA-264 (atrazine), α2-tubulin-239 (trifluraline) and ACCase-1781 (sethoxydim). 2) Resistance to trifluraline was not high enough to allow efficient weed control without crop damage, in contrast to resistance to atrazine and sethoxydim, which allowed further breeding and commercial release. However, trifluralin resistance can be used to maintain purity of male sterility lines. Yield of sethoxydim-resistant germplasm was even increased with respect to isogenic susceptible material. 3) A pollen dispersal curve was measured. Both the wild relative and adjacent foxtail millet plants could be cross-fertilized at low frequency in the field. Phenotype admixture in adjacent fields was observed with the dominant gene only, the maternal resistance exhibiting the lowest dispersal risk.