Amyloids, found as extracellular protein deposits in a diverse group of human and animal disorders, are characterized by a basic scaffold consisting of cross ß-sheet structure. Both far-UV circular dichroism and Fourier transform infrared spectroscopy (FTIR) spectroscopies are the most commonly used techniques for determining the secondary structure of proteins and peptides that either have not been or cannot be studied by nuclear magnetic resonance or X-ray crystallography. Both techniques are complementary and preferentially used depending on the physical state of the analyte and the major secondary structure element. Although there are special setups for working with films, circular dichroism is best suited for diluted solutions of polypeptides exhibiting α-helix as major structural element. On the other hand, FTIR works best with concentrated solutions, solids, and films and resolves with accuracy the ß-sheet composition. Both spectroscopies need a small amount of protein for analysis, are non-destructive and can monitor very accurately relative changes owing to the influence of environment of the sample, though display interferences with some widely used chemicals. Within the amyloid field, conjunction of both spectroscopies has provided the first filter step for amyloid detection and has contributed to decipher the structural aspects of the amyloid formation mechanism.