The information provided by completely sequenced genomes of methanogens can yield insights into a deeper molecular understanding of evolutionary mechanisms.This review describes the advantages of using metabolic pathways to clarify evolutionary correlation of methanogens with archaea and prokaryotes.Metabolic trees can be used to highlight similarities in metabolic networks related to the biology of methanogens.Metabolic genes are among the most modular in the cell and their genes are expected to travel laterally,even in recent evolution.Phylogenetic analysis of protein superfamilies provides a perspective on the evolutionary history of some key metabolic modules of methanogens.Phage-related genes from distantly related organisms typically invade methanogens by horizontal gene transfer.Metabolic modules in methanogenesis are phylogenetically aligned in closely related methanogens.Reverse order reactions of methanogenesis are achieved in methylotrophic methanogens using metabolic and structural modules of key enzymes.A significant evolutionary process is thought to couple the utilization of heavy metal ions with energetic metabolism in methanogens.Over 30 of methanogens genomes have been sequenced to date,and a variety of databases are being developed that will provide for genome annotation and phylogenomic analysis of methanogens.Into the context of the evolutionary hypothesis,the integration of metabolomic and proteomic data into large-scale mathematical models holds promise for fostering rational strategies for strain improvement.