During the early 13th century, a group of European children traveled to the Holy Land to spread the word of Christ. This became known as The Children's Crusade. Over the centuries, the precise nature of the crusade has been obscured by myth and legend. Many historians believe that the crusaders were actually poor people, rather than children. In any case, according to traditional accounts, the Children's Crusade was led by a boy, allegedly inspired by a vision of Jesus who told him to go to the Holy Land and peacefully convert Muslims to Christianity.

In relation to Slaughterhouse-Five, the subtitle has two possible meanings. The original Children's Crusade dissolved into tragic failure, with many of those involved being killed or sold into slavery. Slaughterhouse-Five is an anti-war novel, which highlights the senseless loss of innocent life that armed conflict always entails. We can see, then, close parallels between the two events.

The second possible meaning comes directly from the book itself. The soldier narrator promises the wife of one of his comrades that he'll call the book he's writing The Children's Crusade as he wants to highlight the futility and bloodshed of war. The title suggests not the heroism displayed in war, but the sacrifice of young, innocent lives, and is therefore entirely appropriate.