High-energy physicists try to decompose matter into its most fundamental pieces by colliding particles at extreme energies. But to extract clues about the structure of matter from these collisions is not a trivial task, due to the incomplete data we can gather regarding the collisions, the subtlety of the signals we seek and the large rate and dimensionality of the data. These challenges are not unique to high energy physics, and there is the potential for great progress in collaboration between high energy physicists and machine learning experts. I will describe the nature of the physics problem, the challenges we face in analyzing the data, the previous successes and failures of some ML techniques, and the open challenges.