The opening of hard X-ray free-electron laser facilities, such as the Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory in the United States, has ushered in a new era in structural determination. With X-ray pulse durations down to 10 fs or shorter, and up to 10(13) transversely coherent photons per pulse in a narrow spectral bandwidth, focused irradiances of 10(18) to 10(21) W cm(-2) or higher can be produced at X-ray energies ranging from 500 eV to 10 keV. New techniques for determining the structure of systems that cannot be crystallized and for studying the time-resolved behavior of irreversible reactions at femtosecond timescales are now available.