Desmosine (1) and isodesmosine (2) are 1,3,4,5- and 1,2,3,5-tetrasubstituted pyridiniums and exist only in the extracellular matrix protein elastin as major crosslinking amino acids. They are formed by the condensation and cyclization of one lysine and three allysines, generated from lysine by lysyl oxidase. Since the discovery of desmosines in 1964, there have been no reports on their chemical synthesis for decades. The first total synthesis of 1 was reported in 2012 and since then, isodesmosine (2), desmopyridine (3), isodesmopyridine (4), neodesmosine (5), and merodesmosine (6) have been synthesized. Isotopically labeled desmosines have also been synthesized for the precise analysis of desmosines using isotope-dilution LC–MS/MS analysis. Synthesis of conjugates with desmosines and carrier proteins was achieved for antibody production. This review summarizes a series of desmosine syntheses based on cross-coupling reactions and Chichibabin pyridinium synthesis as synthesis methodologies. The obtained results would help in the development of novel diagnostic and therapeutic methodologies for elastin-degradation-related diseases.