The formation of monolayers begins with interaction between the polar part ("head") of individual molecules and the substrate surface. Subsequent ordering of molecules in the layer's plane – self-assembly of the layer – occurs due to the Van der Waals interactions between the hydrophobic parts of molecules ("tails"). A variety of materials (silicon, metals, oxides) can be used as substrates. The substrate's surface can be flat (as in conventional materials) or curved (if the substrate is in the form of nanoparticles).

Historically, the first example of self-assembling monolayers was the Langmuir-Blodgett films (1935). The term "self-assembly" was introduced in 1983 when the phenomenon of close packing of alcantiols monolayers on gold surface was discovered (see the Figure).

The formation of monolayers of amphiphilic molecules is used for the protection or modification of various surfaces, e.g. to change their character from hydrophilic to hydrophobic. Self-assembling monolayers are also used in molecular nanoelectronic devices and nanoelectromechanical systems.