The Antarctic icefishes (Family Channichthyidae) provide excellent examples of unique traits that can arise in a chronically cold and isolated environment. Their loss of hemoglobin (Hb) expression, and in some cases, loss of myoglobin (Mb) expression, has taught us much about the function of these proteins. Although absences of the proteins are fixed traits in icefishes, the losses do not appear to be of adaptive value. Contrary to some suggestions, loss of Hb has led to higher energetic costs for circulating blood, and losses of Mb have reduced cardiac performance. Moreover, losses of Hb and Mb have resulted in extensive modifications to the cardiovascular system to ensure adequate oxygen delivery to working muscles. Recent studies suggest that losses of Hb and Mb, and their associated nitric oxide (NO)-oxygenase activities, may have accelerated the development and evolution of these cardiovascular modifications. The high levels of NO that should occur in the absence of Hb and Mb have been shown in other animal groups to lead to an increase in tissue vascularization, an increase in the lumenal diameter of blood vessels, and an increase in mitochondrial densities. These characteristics are all hallmark traits of Antarctic icefishes. Homeostatic feedback mechanisms thus may have accelerated evolution of the pronounced cardiovascular traits of Antarctic icefishes.