The phospho-aldol reaction is a well-known and increasingly exploited synthetic process for the construction of phosphorus-carbon bonds. The reaction, essentially a base-catalysed addition reaction between a hydrogen-phosphonate ester and a carbonyl substrate, affords alpha-(α)-functionalised phosphonate esters. Such molecular scaffolds offer considerable scope in medicinal chemistry as the basis for new enzyme inhibitors. Since the 1950s there have been many variants of the basic phospho-aldol reaction published for the stoichiometric synthesis of α-functionalised phosphonates, but most recently attention has shifted to the control of asymmetry in the transformation. It has been shown that the biological properties of α-functionalised phosphonates are influenced by their stereochemistry. This report summarises the developments in asymmetric catalytic variants of the phospho-aldol reaction tracing their evolution from early studies in the 1980s to the current day whilst attempting to suggest future advances within the context of growing applications in biomedical science.