The classic 1953 paper by Frank presented a mathematical mode of autocatalysis that provides a "simple and sufficient life model" leading ultimately to homochirality over many autocatalytic cycles, as illustrated in Scheme 1. The two key features of this theoretical model are: 1) each enantiomer of a molecule is able to self-replicate and, importantly, 2) each enantiomer is able to suppress, or partially suppress, the replication of its mirror image. This second aspect is accomplished by what Frank termed "mutual antagonism", which is key to the amplification of enantiomeric excess (ee) over many cycles. Frank's paper ended with the rather understated observation that an experimental demonstration of his mathematical model "may not be impossible." As later noted by Wynberg, this simple statement served as a call to arms to "every red-blooded synthetic organic chemist." Here we review the chronology of attempts to demonstrate the Frank autocatalytic model for the emergence of homochirality and to assess the prebiotic plausibility of such systems. = deactivated enantiomers Asymmetric Amplification: 20% ee è 33% ee è 50% ee è 67% ee Frank model. Initially, most work focused on point 1, autocatalysis, rather than point 2, an inhibition mechanism. Sigmoidal product concentration profiles have often been presented as evidence of autocatalysis. However, sigmoidal kinetic behavior can arise from other causes, which, as shown in Scheme 2, commonly include catalyst activation 8 and product-induced rate acceleration. 9 Scheme 2. Reaction networks exhibiting sigmoidal profiles. a) authentic autocatalysis, where product C catalyzes its own formation; b) catalyst activation, where a pre-catalyst pre-cat reacts to form the active catalyst cat over the course of the reaction; c) product acceleration, where reaction product C binds to the catalyst cat to form a more efficient catalyst cat*. Although all three reaction networks may exhibit sigmoidal kinetic profiles, only an authentic autocatalytic reaction system has the potential to lead to homochirality from a small initial imbalance.