While I would not have written this some years back, now when faced with a tricky problem indexing a powder diffraction pattern, I would today ask if one should even try. A variant of electron microscopy known as MicroED has advanced tremendously, and for many materials, not only can electron diffraction be used with a powder specimens to obtain the unit cell constants, but also to collect a diffraction data set that can be used to solve the structure. Once that is done, there is still great value in further refining the structure against x-ray and/or neutron data, as electron diffraction has significant problems with obtaining accurate intensity values for structure factors due to dynamical electron diffraction, but this is not the case with x-rays and neutrons. Thus, there are significant advantages in using electron diffraction on unknown materials in combination with x-rays. There are instruments designed specifically for measuring electron diffraction, but more some general purpose many transmission electron microscopes (TEM) can also be used. These are very expensive instruments, but some institutions make them available for external use and at other locations collaboration with the microscopists is welcomed.