Applications of synchrotron X-ray diffraction techniques have enabled crystallographic characterization of pressure-induced phase transitions in diamond anvil cells (DACs) at megabar pressures. Accurate determination of high-pressure structures is crucial for understanding all other pressure-induced property changes. This chapter discusses current capabilities, technical challenges, and future perspectives of the multigrain techniques for high-pressure studies. Through single-crystal structure analysis of seifertite SiO2 at 129 GPa, we conclude that single-crystal structure determination and refinement is possible in general cases at megabar pressures. A nearly full convergence of the structure can be achieved applying the multigrain method, and high-quality crystallographic data can then be obtained. In addition, multigrain indexation can be applied for fast online analysis of multiphase systems during synchrotron sessions. Future development of software will certainly promote wide application of the multigrain techniques. The multigrain capabilities can be further extended to multimegabar pressures. Combination of in situ X-ray powder diffraction, multigrain indexation, and single-crystal structure determination on individual grains provides new opportunities to characterize new phases at megabar pressures and beyond.