Mathematics has its famous Millennium Problems (and, historically, Hilbert's 23), questions that helped to shape the direction of the field.
I have little idea, though, what the Riemann Hypotheses and P vs. NP's of statistics would be.
So, what are the overarching open questions in statistics?
Edited to add: As an example of the general spirit (if not quite specificity) of answer I'm looking for, I found a "Hilbert's 23"-inspired lecture by David Donoho at a "Math Challenges of the 21st Century" conference: High-Dimensional Data Analysis: The Curses and Blessings of Dimensionality
So a potential answer could talk about big data and why it's important, the types of statistical challenges high-dimensional data poses, and methods that need to be developed or questions that need to be answered in order to help solve the problem.