When the first solid‐state NMR structure determination strategies were developed, it was intuitively clear that they needed to be analogous to the solution NMR scheme: produce isotopically enriched protein sample, make site‐specific assignments, determine structure‐defining restraints, calculate a structure using a simulated annealing protocol, and then iterate through the previous steps to refine the structure. However, there are solid‐state‐specific issues that need to be considered when deriving protocols for biomolecular structure determination, as outlined in this chapter. First of all, it is not trivial to produce resolved spectra, which led to the use of nano‐ or microcrystalline samples of soluble proteins. Most structure determination protocols were initially tested on such samples, providing a proof of principle and a direct comparison with proteins of known structure determined by solution NMR and X‐ray crystallography. This chapter reviews these protocols, starting with the preparation of nano‐ or microcrystalline samples, and presenting strategies for obtaining sequential assignments and restraint collection. At the end, the results of the initial structure determination projects are compared.