The celebrated Michaelis–Menten (MM) expression providesa fundamental relation between the rate of enzyme catalysisand substrate concentration. The validity of this classicalexpression is, however, restricted to macroscopic amounts ofenzymes and substrates and, thus, to processes with negligiblefluctuations. Recent experiments have measured fluctuationsin the catalytic rate to reveal that the MM equation,though valid for bulk amounts, is not obeyed at the molecularlevel. In this review, we show how new statistical measuresof fluctuations in the catalytic rate identify a regime in whichthe MM equation is always violated. This regime, characterizedby temporal correlations between enzymatic turnovers,is absent for a single enzyme and is unobservably short in theclassical limit.