This review considers the history of genosystematics (macromolecular systematics) from early studies of E. Chargaff and A.N. Belozersky up to the present, with emphasis on the most important discoveries in the field. The potential and limitations of genosystematics and possible ways of further development are analyzed using plants as an example. The future of genosystematics depends to a great extent on adequate employment of its methods in studying the problems of phylogeny and taxonomy. Analysis of recent publications shows that this requirement is not always met. It is no less important to design and improve the methods of genosystematics, especially those for comparing complete genomes.