Lysine cannot be synthesized by mammals and, as a consequence, is an indispensable amino acid. The main role of lysine is to participate in protein synthesis. The catabolism of lysine is principally located in the liver. Lysine released from digested protein undergoes a significant first-pass metabolism of approximately 30 to 42% in humans and piglets. An important question regarding the biological basis of the requirement of lysine is the possible participation of microbial de novo synthesized amino acids in the whole-body fluxes. Recent intake recommendations to meet the lysine requirement range from 64 to 30 mg/(kg.d) for 0.5-y infants and adults (>18 y), respectively. Lysine intake in the Western human diet is in the range 40-180 mg/(kg.d). An upper limit of 300-400 mg/(kg.d) can be considered in humans.