Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to this challenge, we will gain profound insights into what makes us human, develop new treatments for brain diseases, and build revolutionary new computing technologies that will have far reaching effects, not only in neuroscience. Scientists at the European Human Brain Project-set to announce more than a dozen new research partnerships worth Eur 8.3 million in funding later this month-the Allen Institute for Brain Science, and the US BRAIN Initiative are developing new paradigms for understanding how the human brain works in health and disease. Today, their international and collaborative projects are defined, explored, and compared during "Inventing New Ways to Understand the Human Brain," at the 2014 AAAS Annual Meeting in Chicago.