Amyloid fibrils are filamentous, β -sheet-rich protein aggregates that are implicated in numerous diseases, including Alzheimer's, Parkinson's, Huntington's, and Type II Diabetes. Because of their insoluble and non-crystalline nature, conventional structural characterization methods such as X-ray crystallography and solution-state nuclear magnetic resonance (NMR) spectroscopy cannot be used to determine the molecular structure of fibrils. Fortunately, advances in solid-state NMR (ssNMR) and cryogenic electron microscopy (cryo-EM) have enabled the determination of high-resolution structures of amyloid fibrils prepared in vitro, as well as those harvested from the tissues of patients. These studies indicate that fibrils share a common conformational motif known as a "cross-β" structure, in which extended β -sheets stack together with their strands aligned perpendicularly to the fibril's long axis. They also demonstrate that fibrils exhibit polymorphism, where a given peptide is capable of forming a variety of distinct fibril structures. Despite the wealth of high-resolution structural information gleaned from ssNMR and cryo-EM, these techniques are not without their pitfalls. Solid-state NMR, for example, requires high sample loads (> 10 mg), expensive isotopic labeling schemes, and long spectral acquisition times that can take several days. To obtain high-resolution structural data, both ssNMR and cryo-EM require relatively extensive sample preparation to ensure that fibrils are both homogeneous and well-ordered. This can introduce bias in determining the molecular structure of amyloids by preferentially selecting for the most abundant fibril polymorphs. In addition, it can be difficult to resolve electron densities in cryo-EM or obtain good chemical shift dispersion in ssNMR for all but the most well-ordered regions of fibrils. Disordered, dynamic, or structurally heterogeneous regions, which could play impor-tant roles in initiating aggregation, sequestering other proteins into amyloid plaques, or aberrantly interacting with biological cells, can be difficult to study with these techniques.