In the late 19th century, it was discovered that legumes can establish a root nodule endosymbiosis with nitrogen-fixing rhizobia. Soon after, the question was raised whether it is possible to transfer this trait to non-leguminous crops. In the past century, an ever-increasing amount of knowledge provided unique insights into the cellular, molecular, and genetic processes controlling this endosymbiosis. In addition, recent phylogenomic studies uncovered several genes that evolved to function specifically to control nodule formation and bacterial infection. However, despite this massive body of knowledge, the long-standing objective to engineer the nitrogen-fixing nodulation trait on non-leguminous crop plants has not been achieved yet. In this review, the unsolved questions and engineering strategies toward nitrogen-fixing nodulation in non-legume plants are discussed and highlighted.