From a strategic perspective the initial significance of the atomic bomb was to skew air warfare even further toward the attacking side. As early as the Thirties, strategic bombing had been understood to favor attackers -- the phrase at the time was "the bomber will always get through" -- but the likes of Tokyo and Dresden required massive effort, hundreds of bombers flying near-concurrent sorties. After the invention of the atomic bomb, that was no longer true -- bomber groups that earlier would have been considered trivial now could destroy cities. Suddenly there was no acceptable penetration of air defenses.

Still, defensive efforts continued. Surface-to-air missiles were a great improvement over anti-aircraft gunnery, and nuclear-armed missiles like the AIM-26 were intended to provide high kill probabilities in a defensive role or even take out entire formations at a shot. The development of ICBMs in the late Fifties and early Sixties may have led to more extensive changes in strategy; these could not be effectively stopped by air defenses (though anti-ballistic missile programs continued until the START treaties killed them), leaving mutually assured destruction as the main defensive option.