Understanding the surface chemistry of TiO2 is key to the development and optimisation of many technologies, such as solar power, catalysis, gas sensing, medical implantation, and corrosion protection. In order to address this, considerable research effort has been directed at model single crystal surfaces of TiO2. Particular attention has been given to the rutile TiO2(110) surface because it is the most stable face of TiO2. In this critical review, we discuss the chemical reactivity of TiO2(110), focusing in detail on four molecules/classes of molecules. The selected molecules are water, oxygen, carboxylic acids, and alcohols-all of which have importance not only to industry but also in nature (173 references).