More than half of the global oil reserves are in carbonate reservoirs. Carbonate rocks, however, in most cases tend to be mixed-wet or oil-wet. Wettability alteration of carbonate reservoir rock has been proven to increase oil recovery significantly. Several chemicals have shown their effect on wettability; however, selection of an appropriate wettability modifier should be made on the basis of the underlying mechanisms and their behavior at reservoir conditions. This review discusses techniques that can help in assessing wettability alteration or reflect on the underlying mechanism and describes several categories of wettability modifiers focusing on their structure-property relationship and factors affecting their performance at reservoir conditions. Surfactants, nanoparticles, salts, and alkalis are four major categories of wettability modifiers that are discussed in this review. Among surfactants, gemini surfactants have great potential and could be a major focus of future research in this area. Nanoparticles are relatively novel materials for wettability alteration with the capability to reduce contact angle significantly at low cost. This review also identifies the current and future challenges related to the performance of various wettability modifiers at high-temperature and high-salinity conditions.