When avoidance is not an option, the common survival strategy is to enter a period of estivation. This is achieved through (1) behavioral adjustments aimed at creating a more stable environment, (2) physiological adjustments to reduce water loss and tolerate the accumulation of nitrogenous and respiratory wastes, and (3) molecular and biochemical adjustments aimed towards the suppression of metabolic rate. This final adaptation is perhaps the most important feature of estivation. By slowing energy demanding biochemical rate processes, tissues are capable of conserving metabolic fuel while at the same time reducing the rate of harmful metabolic end-product accumulation. Amongst all the adaptive strategies employed to survive periods of estivation, the suppression of metabolism is the one feature that can extend survival time of the estivator many times beyond that of the other two adjustments alone, and as such, somewhat negates the factor of time. This chapter discusses the physiologic, metabolic, and molecular barriers that fish estivators must surmount to successfully survive chronic periods of drought. In particular, it examines the importance of metabolic suppression and the possible mechanisms by which a reduction in metabolic rate can be achieved under these conditions. Because much of the current literature regarding fish estivation is either anecdotal or limited to a few species, this chapter aims to fill the gaps in knowledge by examining anoxic metabolic arrest in other phylogenetic orders.