Marine life in the polar, especially Antarctic, cold is characterized by a low to moderate pace at permanently low temperatures. This chapter sets out to identify the temperature-dependent trade-offs in the metabolic physiology, biochemistry, and functional genomics of cold adaptation in marine fish and to analyze the implications of these trade-offs for thermal tolerance and performance characteristics at organismal and ecological levels. During cold adaptation, shortage of aerobic capacity at an organismic level is compensated for by enhancing the functional capacity of cells and tissues through mitochondrial proliferation, an upregulation of aerobic enzyme activities and of cellular energy stores (lipids), and associated molecular and membrane adjustments. These compensatory adjustments parallel a downward shift of thermal tolerance windows and, in Antarctic fish, a reduction in baseline energy demands in the cold. These mechanisms also aid recovery rates from exhaustive exercise but are implemented at the expense of reduced anaerobic capacity, seen in moderately active life forms. Significant anaerobic capacity is found only at the low end of the activity spectrum (e.g., among benthic eelpout [Zoarcidae]). Especially in demersal to pelagic Antarctic fishes, among notothenioids, low SMR and enhanced lipid stores, as well as a preference for lipid catabolism, indicate a high energy efficiency of aerobic metabolism at high ambient oxygen availability. In the lower range of performance levels, the same sustainable swimming velocities are achieved in temperate and Antarctic fish, supported by largely elevated numbers of mitochondria in red muscles of Antarctic fish. The accumulation of mitochondrial networks and lipid substrates supports enhanced diffusional oxygen supply and, thereby, further energy savings. ATP synthesis capacities of mitochondria are reduced and the associated drop in mitochondrial proton leakage contributes to low resting oxygen demand. It appears that in a trade-off between space adopted by myofilaments, mitochondria, and sarcoplasmic reticulum, especially the need for more mitochondria for maintained functional capacity in the cold is a major constraint on maximum scope for activity and is linked to lower levels of muscular force per muscle cross-sectional area. Similarly, the capacity of the heart to maintain aerobic scope within the thermal tolerance window is limited, because of the space constraints within cardiomyocytes and the limits on the relative size of the heart. These trends in skeletal and cardiac muscle are synergistic and reflect the limitation of aerobic scope of the whole organism. These constraints are operative, especially in larvae and limit their level of activity and energy expenditure even more than in adults. Furthermore, limited functional capacity at reduced SMR contributes to reduced costs of cold tolerance but, as a trade-off, contributes to the narrow windows of thermal tolerance and low heat tolerance of Antarctic stenotherms. Molecular studies indicate a selective upregulation of aerobic enzyme capacities (e.g., COX or CS) or transmembrane ion exchange (e.g., Na+/K+-ATPase) by transcriptional, translational, and likely, posttranslational control. Kinetic properties of enzyme proteins (especially LDH) are discussed in light of structural modifications at the protein level, with or without slight changes in the primary sequence of the molecule. Either downward or upward shifts of activation enthalpies may reflect their specific role in either facilitation (for functional capacity) or restriction of flux (for control of metabolic costs) through specific metabolic reactions and pathways. Despite overall energy savings, protein synthesis capacities remain cold-compensated, supporting peak summer growth rates in Antarctic species comparable to those seen in temperate species. As a trade-off, baseline metabolic costs and, thus, SMR are reduced for the sake of a maximization of growth rates, especially in benthic fish. Energy-saving strategies are excessive in more active pelagic fish, in which the higher cost of living still causes lower growth at elevated SMRs. Growth maximization may also occur at the expense of reduced energy allocation to other higher functions. Overall, higher functions like exercise capacity and larval development display lower rates in the permanent cold, likely because energy efficiency needs to be enhanced and a maximum of energy allocated to individual growth and to storage supplies for lecithotrophic larvae. These trade-offs and the overproportional buildup of aerobic energy production machinery at low performance capacity may be a general constraint for all faunal elements of polar, especially Antarctic ecosystems, thereby explaining why high-performance (ectotherm) life is rare, if it exists at all, in the permanent cold. © 2005 Elsevier Inc. All rights reserved.