Studies of the history of life provide an interesting case study of how the questions scientists can ask, and from which they expect reliable answers, change over time. Some of these changes reflect the introduction of new technology or methodological advances in other fields that open new opportunities; other changes reflect an evolving perspective on what constitutes important research questions or the integration of multiple streams of information. In this contribution, I consider the changing nature of questions in paleontology, largely focusing on English-speaking paleontologists since the mid-twentieth century. Rather than bemoaning the field’s limitations, paleontologists have pioneered techniques to identify and often correct preservation and collecting biases in the fossil record. Rigorous methods to infer and test phylogenies have been integrated with molecular clock studies to infer branch-points in phylogeny, and with insights from comparative developmental studies, which together inform our understanding of evolutionary dynamics, particularly novelty. Together, these advances have changed the questions paleontologists can address about the history of life, eliminating some questions (particularly in paleoecology), but greatly expanding research programs in other areas as well as collaborations with biologists and other Earth scientists. I suggest that the questions driving paleontologists have evolved from primarily descriptive and explanatory to increasingly analytical and integrative. These trends are briefly illustrated with examples from studies of the Ediacaran-Cambrian diversification of animals, and from studies of mass extinctions.