A recent publication by M. Šako, F. Staniscia, and M. Kanduč in PNAS Nexus unveils the conditions under which lipid monolayers can spontaneously self-assemble on solid substrates. Although it has long been known that this process requires a sufficiently hydrophobic surface, a precise quantitative “hydrophobicity threshold” had not been established. The study has now shown that the crucial factor in determining monolayer formation is the surface contact angle, which should exceed the threshold value of 65±5°. This universal insight serves as a guiding principle for using lipid monolayers as surface coatings in diverse applications, such as enhancing biocompatibility and preventing undesired adhesion.