Inland waters, especially lakes are important methane sources to the atmosphere, which contributed to 40% of the total methane production from the global natural ecosystems. The methanogens and methanotrophs play key roles in the reactions of methane productions and consumptions in lake ecosystems. New discoveries of methane generation and oxidation progress in lake environments have been reviewed in this manuscript, in which the emphasis was put on the distribution, metabolism and regulation of methanogens and methanotrophs in natural lakes. The current researchers found that the methane in lakes is produced not only by the methanogens lived in the sediment and anaerobic water layer, but also by the microbes survived in the aerobic water. Current knowledge was consensus that most of the methane was oxidized by the methane oxidation process and transformed into carbon dioxide, methanol, formaldehyde or formic acid before it escaping from the water. Besides the traditional methane oxidation based on oxygen reduction, anaerobic oxidation of methane (AOM) was the important supplementary process in natural lakes. Researches indicated there were at least three major AOM processes in lakes, which were sulfate-dependent AOM, nitrite-and nitrate-dependent AOM as well as Fe³⁺/Mn⁴⁺-dependent AOM. Niches separations were identified among different AOM processes, for example, the sulfate-dependent AOM were generally detected in the soda and saline lakes, whereas the nitrite-and nitrate-dependent AOM took place in the freshwater lakes. Water temperature and dissolved oxygen were identified to be the most important factors that significantly influencing the abundance of methanogens and methanotrophs, as well as the community composition of these microbes. Actually, microorganisms participated in the methane production and oxidation could be affected by multiple factors in a certain ecosystem, such as pH, organic matter and salinity. More types of lakes need to be studied in order to reveal the pattern of the spatial-temporal distribution of methanogens and methanotrophs and the mechanisms of metabolism regulation.