The existence of intermolecular forces was first postulated by
Johannes Diderik van der Waals in 1873. However, Nobel laureate
Hermann Emil Fischer developed supramolecular chemistry's philosophical roots. In 1894,
 Fischer suggested that
enzyme-substrate interactions take the form of a "lock and key", the fundamental principles of
molecular recognition and
host-guest chemistry. In the early twentieth century noncovalent bonds were understood in gradually more detail, with the hydrogen bond being described by
Latimer and Rodebush in 1920.
The use of these principles led to an increasing understanding of
protein structure and other biological processes. For instance, the important breakthrough that allowed the elucidation of the
double helical structure of
DNA occurred when it was realized that there are two separate strands of nucleotides connected through hydrogen bonds. The use of noncovalent bonds is essential to replication because they allow the strands to be separated and used to template new double stranded DNA. Concomitantly, chemists began to recognize and study synthetic structures based on noncovalent interactions, such as
Eventually, chemists were able to take these concepts and apply them to synthetic systems. The breakthrough came in the 1960s with the synthesis of the
crown ethers by
Charles J. Pedersen. Following this work, other researchers such as
Donald J. Cram,
Jean-Marie Lehn and
Fritz Vögtle became active in synthesizing shape- and ion-selective receptors, and throughout the 1980s research in the area gathered a rapid pace with concepts such as mechanically interlocked molecular architectures emerging.
The importance of supramolecular chemistry was established by the 1987
Nobel Prize for Chemistry which was awarded to Donald J. Cram, Jean-Marie Lehn, and Charles J. Pedersen in recognition of their work in this area.
 The development of selective "host-guest" complexes in particular, in which a host molecule recognizes and selectively binds a certain guest, was cited as an important contribution.
In the 1990s, supramolecular chemistry became even more sophisticated, with researchers such as
James Fraser Stoddart developing
molecular machinery and highly complex
self-assembled structures, and
Itamar Willner developing sensors and methods of electronic and biological interfacing. During this period,
photochemical motifs became integrated into supramolecular systems in order to increase functionality, research into synthetic self-replicating system began, and work on molecular information processing devices began. The emerging science of
nanotechnology also had a strong influence on the subject, with building blocks such as
dendrimers becoming involved in synthetic systems.