High capacity for fatty acid (FA) oxidation is a sign of metabolic fitness and is important not only for exercise performance but also for health promotion. FA oxidation is controlled by multiple mechanisms e.g. substrate availability, transport over sarcolemma and transport into mitochondrial matrix. FA oxidation increases with the intensity of the exercise but reaches a peak at about 40– 60% of VO2max after which it is reduced. The mechanism for the crossover from FA to CHO at high exercise intensities is not fully understood. One hypothesis is that increased glycolytic flux may limit the carnitine-mediated transport of FA into mitochondrial matrix through inhibition of carnitine-palmitoyl transferase (CPT1). Supporting evidence is the observed trapping of carnitine as acetyl-carnitine and inhibition of CPT1 by acidosis. Fuel interaction may also be under control of cellular energy state. The apparent affinity of mitochondrial respiration for ADP is lower for FA than for pyruvate, which will favour FA oxidation at low but CHO at high exercise intensities. Further control by energy state may occur at pyruvate dehydrogenase and acyl-CoA synthetase. Recent studies demonstrate that additional control of FA oxidation is exerted downstream of CPT1 within mitochondria. Studies on isolated mitochondria show that the maximal rate of respiration with palmitoyl-carnitine (PC) (bypasses CPT1) is (i) influenced by muscle fibre type, (ii) increases after extreme exercise and (iii) is related to whole body FA oxidation during low-intensity exercise. The limitation of mitochondrial oxidation of PC and the interaction between CHO and FA oxidation are unclear and further studies are warranted.