The interaction between molecules and solid surfaces plays important roles in various applications, including catalysis, sensors, nanoelectronics, and solar cells. Surprisingly, a full understanding of molecule–surface interaction at the quantum mechanical level has not been achieved even for very simple molecules, such as water. In this mini-review, we report recent progresses and current status of studies on interaction between representative molecules and surfaces. Taking water/metal, DNA bases/carbon nanotube, and organic dye molecule/oxide as examples, we focus on the understanding on the microstructure, electronic property, and electron–ion dynamics involved in these systems obtained from first-principles quantum mechanical calculations. We find that a quantum mechanical description of molecule–surface interaction is essential for understanding interface phenomenon at the microscopic level, such as wetting. New theoretical developments, including van der Waals density functional and quantum nuclei treatment, improve further our understanding of surface interactions.