In 1900, the British physicist Lord Kelvin is said to have pronounced: "There is nothing new to be discovered in physics now. All that remains is more and more precise measurement." Within three decades, quantum mechanics and Einstein's theory of relativity had revolutionized the field. Today, no physicist would dare assert that our physical knowledge of the universe is near completion. To the contrary, each new discovery seems to unlock a Pandora's box of even bigger, even deeper physics questions. These are our picks for the most profound open questions of all.