One hundred years ago, Hill and Lupton introduced the concept of maximal oxygen uptake (V˙O2max), which is regarded as "the principal progenitor of sports physiology." We provide a succinct overview of the evolvement of research on V˙O2max, from Hill and Lupton's initial findings to current debates on limiting factors for V˙O2max and the associated role of convective and diffusive components. Furthermore, we update the current use of V˙O2max in elite endurance sport and clinical settings. Practical Applications and Conclusions: V˙O2max is a healthy and active centenarian that remains a very important measure in elite endurance sports and additionally contributes as an important vital sign of cardiovascular function and fitness in clinical settings. Over the past 100 years, guidelines for the test protocols and exhaustion criteria, as well as the understanding of limiting factors for V˙O2max, have improved dramatically. Presently, possibilities of accurate and noninvasive determination of the convective versus diffusive components of V˙O2max by wearable sensors represent an important future application. V˙O2max is not only an indicator of cardiorespiratory function, fitness, and endurance performance but also represents an important biomarker of cardiovascular function and health to be included in routine assessment in clinical practice.