SummaryHypoxia survival in fish requires a well-coordinated response to either secure more O2 from the hypoxic environment or to limit the metabolic consequences of an O2 restriction at the mitochondria. Although there is a considerable amount of information available on the physiological, behavioral, biochemical and molecular responses of fish to hypoxia, very little research has attempted to determine the adaptive value of these responses. This article will review current attempts to use the phylogenetically corrected comparative method to define physiological and behavioral adaptations to hypoxia in intertidal fish and further identify putatively adaptive biochemical traits that should be investigated in the future. In a group of marine fishes known as sculpins, from the family Cottidae, variation in hypoxia tolerance, measured as a critical O2 tension (Pcrit), is primarily explained by variation in mass-specific gill surface area, red blood cell hemoglobin–O2 binding affinity, and to a lesser extent variation in routine O2 consumption rate (). The most hypoxia-tolerant sculpins consistently show aquatic surface respiration (ASR) and aerial emergence behavior during hypoxia exposure, but no phylogenetically independent relationship has been found between the thresholds for initiating these behaviors and Pcrit. At O2 levels below Pcrit, hypoxia survival requires a rapid reorganization of cellular metabolism to suppress ATP consumption to match the limited capacity for O2-independent ATP production. Thus, it is reasonable to speculate that the degree of metabolic rate suppression and the quantity of stored fermentable fuel is strongly selected for in hypoxia-tolerant fishes; however, these assertions have not been tested in a phylogenetic comparative model.