The recently completed International Space Station (ISS) is among the greatest international cooperative endeavors in the history of science and technology. However, during its construction, some questioned the potential for scientific return from this global investment. Now that construction is complete and the station has entered its research and development phase, we bring together scientists spanning the biological and physical sciences to describe the work they have already done from the ISS and the plans and challenges for the next decade. From vaccines to protect against some of Earth’s trickiest diseases to discoveries that may uncover the nature of dark matter and the structure of the universe, science from the ISS touches all of our lives in ways many of us have never imagined or could have believed possible.