Sears (1956) pioneered plant chromosome engineering 50 years ago by directed transfer of a leaf rust resistance gene from an alien chromosome to a wheat chromosome using X-ray irradiation and an elegant cytogenetic scheme. Since then many other protocols have been reported, but the one dealing with induced homoeologous pairing and recombination is the most powerful, and has been extensively used in wheat. Here, we briefly review the current status of homoeologous recombination-based chromosome engineering research in plants with a focus on wheat, and demonstrate that integrated use of cytogenetic stocks and molecular resources can enhance the efficiency and precision of homoeologus-based chromosome engineering. We report the results of an experiment on homoeologous recombination-based transfer of virus resistance from an alien chromosome to a wheat chromosome, its characterization, and the prospects for further engineering by a second round of recombination. A proposal is presented for genome-wide, homoeologous recombination-based engineering for efficient mining of gene pools of wild relatives for crop improvement.