Abstract Over the last two decades, fluorine substitution has become one of the essential structural traits in modern pharmaceuticals. Thus, about half of the most successful drugs (blockbuster drugs) contain fluorine atoms. In this review, we profile 17 fluorine‐containing drugs approved by the food and drug administration (FDA) in 2018. The newly approved pharmaceuticals feature several types of aromatic F and CF 3 , as well as aliphatic (CF 2 ) substitution, offering advances in the treatment of various diseases, including cancer, HIV, malarial and smallpox infections.