Book excerpt: This research explores the applications of three unnatural amino acids in order to demonstrate their utility in rational protein design. The amino acids are: a photo active amino acid that can cleave the protein backbone using light, an immunogenic amino acid that was developed into a potential therapeutic vaccine for rheumatoid arthritis, and several histidine analog unnatural amino acids which could be used to study enzyme active site histidine catalysis. This research also explores the possibility of creating transgenic mice capable translating exogenously supplied unnatural amino acids. Challenges such as amino acid pharmacokinetics, transgene translation, and generation of transgenic animals are addressed.