Lubricants have played important roles in friction and wear reduction and increasing efficiency of mechanical systems. To optimize tribological performance, chemical reactions between a lubricant and a substrate must be designed strategically. Tribochemical reactions are chemical reactions enabled or accelerated by mechanical stimuli. Tribochemically activated lubricant additives play important roles in these reactions. In this review, current understanding in mechanisms of chemical reactions under shear has been discussed. Additives such as oil-soluble organics, ionic liquids (ILs), and nanoparticles (NPs) were analyzed in relation to the tribochemical reaction routes with elements in metallic substrates. The results indicated that phosphorus, sulfur, fluorine, and nitrogen are key elements for tribochemical reactions. The resulting tribofilms from zinc dithiophosphates (ZDDP) and molybdenum dithiocarbamate (MoDTC) have been widely reported, yet that from ILs and NPs need to investigate further. This review serves as a reference for researchers to design and optimize new lubricants.