Abstract This review aims to summarize the changes of the NOS/NO system which occur in the lungs, gills, kidney, heart, and myotomal muscle of air breathing fish of the genus Protopterus , i.e. P. dolloi and P. annectens , in relation to the switch from freshwater to aestivation, and vice-versa. The modifications of NOS and its partners Akt and Hsp-90, and HIF-1α, detected by immunohistochemical and molecular biology methods, are discussed together with the apoptosis rate, evaluated by TUNEL. We hypothesize that these molecular components are key elements of the stress-induced signal transduction/integration networks which allow the lungfish to overcome the dramatic environmental challenges experienced at the beginning, during, and at the end of the dry season. [ABSTRACT FROM AUTHOR]