Frictional properties of monolayers formed from 11 double-chain quaternary ammonium surfactants self-assembled onto mica were measured using lateral force microscopy. Frictional forces differ by orders of magnitude and can increase or decrease with increasing humidity, and frictional force vs velocity curves in some cases display maximum. These differences correlate at a molecular level with variations in the surfactant’s chemical composition, degree of unsaturation, chain length, and omega functional group. These differences can also be directly related to the monolayer’s structure, phase transition temperature, compressibility and surface hydrophobicity as determined by X-ray diffraction, scanning calorimetry, contact angle, and simulation data. Comparison between lateral force measurements using a standard AFM tip and measurements modified by replacing the tip with a sphere provide a relationship between nanoscale and microscale frictional properties. These observations establish a relation between frictional properties and molecular properties of thin films which are important in many applications including lubrication and tribology.