During the last decades, the bottom–up strategy of on-surface molecular reactions has been extensively investigated in order to fulfill controllable fabrication of covalent interlinking nanostructures/nanomaterials at atomic scale. A variety of organic reactions have been introduced to substrates, such as Ullmann coupling, Glaser coupling, cyclodehydrogenation and so on. In this paper, these on-surface molecular reactions will be reviewed from three aspects: the precursor, surface and external stimuli. Finally, a summary of past achievements and an outlook of future scientific challenges will be discussed.