Advances in the materials technology, and novel manufacturing techniques greatly enhanced the potential for structural unitization to simplify assembly of airplane structure. However, the challenges of maintaining an acceptable level of structural robustness, with reduced damage tolerance capability inherent to the integral construction, require the designers to well comprehend and appreciate unique properties of monolithic structure. Historic evolution of the airplane structural integrity concepts is reviewed. Then, the current state of durability and damage tolerance, and the different approaches employed in the current military (USAF) and commercial transport airplanes are discussed. The effect of Widespread Fatigue Damage (WFD) on the Fail-Safe structure, and the need for advancing the traditional Fail-Safe design approaches, are discussed. Some valuable lessons learned from tragic accidents are also discussed, with the Lusaka accident as an example. Then finally, the issues and challenges of designing the airplane structure in unitized construction are discussed. Some experimental results are presented as a part of the discussion.