Multidisciplinary Design Optimization (MDO) of flight vehicles is now a focus of international research in the aerospace field. The engineering application research of MDO, however, falls behind the fundamental theoretical research domestically, which sometimes even leads to the suspicion of the practicability of MDO. On the basis of our research on MDO in the past decade, the difficulties of the engineering application and the relevant key technologies of MDO were analyzed. The international research on engineering application of MDO can be approximately summarized into three stages, the characteristics of which were illustrated with three application examples in flight vehicle design implemented by our group. Finally, the future trends of the MDO engineering application were briefly analyzed.