Higher levels of fitness are associated with reduced risk of a wide variety of illnesses and chronic conditions. For cardiovascular disease (CVD) and many metabolic conditions, the fitness-morbidity/mortality curve is not linear but curvilinear, with lower levels of fitness being associated with significantly higher levels of risk compared to moderate and high levels of fitness. We have a very poor understanding of what the low fit phenotype represents as it is clearly more than just low physical activity levels. For example, there are likely some metabolic disadvantaged individuals with intrinsically low fitness and low oxidative capacity that are also prone to being sedentary due to easy fatigability. For these individuals, there exists a worse case scenario of a sedentary lifestyle superimposed on metabolically disadvantaged muscle resulting in the exaggerated CVD and metabolic risk. There is clearly a need for more work exploring the risk associated with low fitness and developing strategies to address the risk of low fitness. For example, we need to (i) define the mechanisms responsible for the exceptional risk associated with being low fit, (ii) identify best physical activity programs for reversing low fitness, (iii) examine whether exercise training nonresponders receive health benefits from exercise training despite the failure to improve fitness, and (iv) explore methods to identify individuals with the "low fit" phenotype without conducting a maximal exercise test. Individuals in the low fit category typically account for the majority of accumulated metabolic/CVD events, thus reducing this risk in this category would have substantial public health and clinical payoff.