Amino acids synthesized in ancestral conditions and/or brought by meteorites may represent the first biomolecules that appeared on Earth. They are precursors for short peptide and amyloid formation with catalytic activities, thus accelerating synthesis of other biomolecules. The synthesis of small catalytic RNAs and their involvement in the appearance of other biomolecules may have represented another step in the direction of the organization of matter at the basis of what would become the ancestors of the first living organisms. The synthesis of such small RNAs would have represented in addition a step toward capacity to store genetic information in complex macromolecules, such complexity culminating in the synthesis of DNA as the carrier of genetic information. Of note, both RNAs and DNA require specific amino acids for their synthesis. The Last Universal Common Ancestor is a theoretical construction, which is proposed to be at the origin of the prokaryotic archaeal and bacterial species. These latter prokaryotic organisms are equipped with partially common but also markedly different metabolic pathways for amino acid synthesis. Both archaea and bacteria can use amino acids either transported from the extracellular medium or synthesized intracellularly for the synthesis of macromolecules (proteins, RNAs, DNA), for ATP production, and for the synthesis of numerous bioactive compounds. The endosymbiotic theory, which postulates that the first primitive unicellular eukaryotes were formed from the association between members among Alphaproteobacteria and Asgard archaea, is coherent with emerging metabolic data suggesting cooperation between these cells for amino acid metabolism. Among the ancestral pluricellular forms of animal life, sponges are equipped with an already sophisticated machinery in terms of amino acid metabolism, such metabolism being dependent on the hosted microorganisms. In mammals, including humans, amino acid metabolism can be different according to cell phenotype, but the general metabolic strategy is about the same that in other living cells. In mammals, the 9 amino acids which cannot be synthesized in significant amount compared to the requirements must be obtained from the diet. Comparison between amino acid metabolism in archaeal/bacterial cells and in mammalian cells reveals common metabolic strategy and important capacity for recycling of numerous amino acid-derived compounds for new functions. Mammals can provide amino acids to the hosted intestinal microbes for their metabolism and physiology as well as for communication between them. Conversely, intestinal bacteria produce metabolites from amino acids, which are active on the host’s intestinal cells. Some among these bacterial metabolites are absorbed through the intestinal epithelial cells and modified in the host’s liver giving rise to bioactive co-metabolites.