- Anvilicious: Surprisingly averted, especially given the focus on the Catholic Church.
- Genius Bonus: The story contains a lot of references to Church dogma which are clearer if the reader has a good working knowledge of Catholicism (and Judaism). Likewise, the use of dead languages.
- Harsher in Hindsight: A large portion of the last section's plot has the main character strenuously advocating against euthenasia, arguing that life is too sacred to destroy for "convenient mercy." The author Walter M. Miller would eventually commit suicide.
- I Am Not Shazam: There are some tantalizing hints that the Old Jew may be Leibowitz himself at first (note the Hebrew initials he scrawls on a rock - L.Tz.) but later in the story he denies this and explains he's only a distant relative.
"Sic transit mundus." (Thus passes the world.)
- The fate of Emily/Emma Leibowitz and the trapped people in the shelter Francis finds. And it's implied that the Old Jew who may or may not be Leibowitz himself wanted Francis to find it, if only to put the past to rest.
- The ending. Especially as Joshua dusts off the dirt on his sandals before boarding the Quo Peregrinatur starship as the world plunges into another Flame Deluge, symbolically severing his ties to Earth.
- Abbot Zerchi trying to persuade a mother not to euthanize her child. The child is stated to be so badly burned by the atomic blast that her gender is not apparent until her mother refers to her as such. Also note that the mother is referred to as "the girl," (implying she is very young herself) and has also been diagnosed as so irradiated as to be untreatable.