In a thought-provoking dialogue, Rick Rosner and Scott Douglas Jacobsen explore the evolving challenges to humanism, from historical conflicts with religion to the disruptive potential of artificial intelligence. They discuss the Humanists International Minimum Statement on Humanism, the Luxembourg Declaration on AI and Human Values 2025, and the alignment problem between AI and human ethics. Topics range from brain–computer interfaces and technological augmentation to the possibility of extending human cognition and lifespan. Drawing on examples from science fiction and cultural narratives, they consider how humanist values—reason, compassion, dignity, and freedom—can guide humanity through profound technological and societal transformations.