Quinone methides (QMs) are considered to be highly reactive intermediates because of their aromatization both in chemical and biological systems. Being highly accessible, quinone methides (QMs) have been widely exploited and their concurrent use has been manifested for the synthesis of tertiary and quaternary carbon centers of bioactives, drugs and drug-like molecules. In this feature article, the synthetic routes, structure–reactivity relationships and synthetic applications of quinone methides are discussed. Formation of the intermediates during bioactivation of different chemical entities and possible chemical manifestations leading to their toxicity in biological systems are also covered.