Aquatic areas frequently face hypoxic conditions. In order to get sufficient oxygen to support aerobic metabolism, a number of freshwater fish resort to aerial respiration to supplement gill respiration especially in situations with reduced oxygen availability in the water. In many species a concomitant reduction in gill surface area or in gill perfusion reduces possible loss of aerially acquired oxygen to the water at the gills, but it also compromises the ion regulatory capacity of gill tissue. In consequence, the reduced gill contact area with water requires appropriate compensation to maintain ion and acid-base homeostasis, often with important ramifications for other organs. Associated modifications in the structure and function of the gills themselves, the skin, the gut, the kidney, and the physiology of water exchange and ion-linked acid-base regulation are discussed. In air-breathing fish, the gut may gain particular importance for the uptake of ions. In addition, tissues frequently exposed to environmental air encounter much higher oxygen partial pressures than typically observed in fish tissues. Physostomous fish using the swimbladder for aerial respiration, for example, will encounter aerial oxygen partial pressure at the swimbladder epithelium when frequently gulping air in hypoxic water. Hyperoxic conditions or rapid changes in oxygen partial pressures result in an increase in the production of reactive oxygen species (ROS). Accordingly, in air-breathing fish, strategies of ionoregulation may be greatly modified, and the ROS defense capacity of air-exposed tissues is improved.