Recent research has suggested that stable, native proteins may be encoded by simple sequences of fewer than the full set of 20 proteogenic amino acids. Studies of the ability of simple amino acid sequences to encode stable, topologically complex, native conformations and to fold to these conformations in a biologically relevant time frame have provided insights into the sequence determinants of protein structure and folding kinetics. They may also have important implications for protein design and for theories of the origins of protein synthesis itself.