The Amazon Basin presents a dynamic regime of dissolved oxygen (DO) oscillations, which varies among habitats within the basin, including spatially, daily, and seasonally. Fish species inhabiting these environments have developed many physiological adaptations to deal with the frequent and periodic events of low (hypoxia), or no (anoxia) DO in the water. Cichlid fishes, especially the genus Astronotus (A. ocellatus and A. crassipinnis), are hypoxic‐tolerant species that can survive in very low DO levels for long periods, while adults often inhabit places where DO is close to zero. The present review will focus on some metabolic adjustments that Amazonian fish use in response to hypoxic conditions, which include many strategies from behavioral, morphological, physiological, and biochemical strategies. These strategies include ASR (aerial surface respiration), lip expansion, branchial tissue remodeling, increases in glycolytic metabolism with the increase of blood glucose levels, and increases in anaerobic metabolism with increases of plasma lactate levels. Other groups over evolutionary time developed obligate aerial respiration with changes in pharyngeal and swim bladder vascularization as well as the development of a true lung. However, most species are water‐breathing species, such as A. ocellatus and A. crassipinnis, which are detailed in this study because they are used as hypoxia‐tolerant model fish. Herein, we draw together the literature data of the physiological mechanisms by which these species decrease aerobic metabolism and increase anaerobic metabolism to survive hypoxia. This is the first attempt to synthesize the physiological mechanisms of the hypoxia‐tolerant Astronotus species.