During his tenure as the secretary of defense, Wilson managed the military as though it were a business. He was initially hesitant to bring about change without conferring with the President, so much so, that Eisenhower reputedly said, "Charlie, you run defense. We both can't do it, and I won't do it. I was elected to worry about a lot of other things than the day-to-day operations of a department." Wilson later brought about a programmatic shift in the armed forces in preparation for modern warfare, including expanding research and development, cutting the size of the standing army, and boosting readiness for a nuclear conflict.
After his resignation, which he had intended after four years, Wilson returned to business interests, chiefly General Motors, though he would also serve as chairman of Michigan's advisory committee to the U.S. Commission of Civil Rights.