The 20th Century saw physics and our corresponding understanding of the world around us virtually explode. Relativity and quantum mechanics totally revolutionized the way we describe matter and energy and led to astonishing discoveries and technological advances. In 1900, the electron had just been discovered and the structure of the atom was just being probed. By 2000, we could “see” atoms, use general relativity to correct atomic clocks for use in the GPS system, produce Bose-Einstein condensates at nano-Kelvin, detect signatures of the big bang, and countless other scientific marvels without parallel in human history. But are the paradigms of 20th century physics still robust and useful for the challenges of the 21st century? As Neils Bohr famously said “Prediction is very difficult, especially if it’s about the future.” (sometimes wrongly attributed to Yogi Bera) so I will avoid that trap to the degree possible. Instead, I will ruminate about the amazing progress in physics in the past and suggest some of the big challenges that lie ahead in which complexity may play an important role.