This mini-review by Inoue, Sumii, and Shibata provides an overview of the prevalence and structural motifs of fluorine-containing pharmaceuticals (fluoro-pharmaceuticals). The authors highlight that about 20% of commercial pharmaceuticals are fluoro-pharmaceuticals, with the first such drug, Florinef, introduced in 1954. The review categorizes 340 fluoro-pharmaceuticals based on their chemotypes, therapeutic purposes, and the presence of heterocycles or chirality. Key findings include: 1. **Prevalence and Trends**: Fluoro-pharmaceuticals have maintained a significant presence in the market, with an increasing number of approvals over the past decades. In 2019, 13 new fluoro-pharmaceuticals were approved by the FDA, accounting for 41% of all small-molecule drugs. 2. **Chemotypes**: The most common chemotypes are Ar–F (45.3%), alkyl–CRF (14.9%), aryl–CF3 (14.6%), Het–F (5.4%), and Het-CF3 (2.7%). Monofluorinated moieties (67.2%) are more prevalent than trifluoromethyl groups (19.2%). 3. **Therapeutic Purposes**: Fluoro-pharmaceuticals are widely used in various therapeutic areas, including gastrointestinal and metabolism, blood and hematopoietic organs, circulatory system, skin disease remedy, urogenital system, and sex hormones. 4. **Heterocycles**: While heterocyclic compounds with fluorinated groups are promising, their diversity is limited. The most common heterocycles are 6-membered heteroaromatics with two nitrogen atoms (pyrimidine, pyrazine, pyrimidone) and one nitrogen atom (pyridine, quinolone, cytosine). 5. **Chirality**: Chiral fluoro-pharmaceuticals, which account for 18% of all fluoro-pharmaceuticals, are less common. Synthetic methodologies for chiral fluorinated drug candidates need further development. The authors conclude that the potential of fluoro-pharmaceuticals is expected to increase with advancements in fluorine chemistry and synthetic methods, particularly in the synthesis of fluorinated heterocyclic compounds. They emphasize the importance of continued research in this area to enhance the development of novel fluoro-pharmaceuticals.This mini-review by Inoue, Sumii, and Shibata provides an overview of the prevalence and structural motifs of fluorine-containing pharmaceuticals (fluoro-pharmaceuticals). The authors highlight that about 20% of commercial pharmaceuticals are fluoro-pharmaceuticals, with the first such drug, Florinef, introduced in 1954. The review categorizes 340 fluoro-pharmaceuticals based on their chemotypes, therapeutic purposes, and the presence of heterocycles or chirality. Key findings include: 1. **Prevalence and Trends**: Fluoro-pharmaceuticals have maintained a significant presence in the market, with an increasing number of approvals over the past decades. In 2019, 13 new fluoro-pharmaceuticals were approved by the FDA, accounting for 41% of all small-molecule drugs. 2. **Chemotypes**: The most common chemotypes are Ar–F (45.3%), alkyl–CRF (14.9%), aryl–CF3 (14.6%), Het–F (5.4%), and Het-CF3 (2.7%). Monofluorinated moieties (67.2%) are more prevalent than trifluoromethyl groups (19.2%). 3. **Therapeutic Purposes**: Fluoro-pharmaceuticals are widely used in various therapeutic areas, including gastrointestinal and metabolism, blood and hematopoietic organs, circulatory system, skin disease remedy, urogenital system, and sex hormones. 4. **Heterocycles**: While heterocyclic compounds with fluorinated groups are promising, their diversity is limited. The most common heterocycles are 6-membered heteroaromatics with two nitrogen atoms (pyrimidine, pyrazine, pyrimidone) and one nitrogen atom (pyridine, quinolone, cytosine). 5. **Chirality**: Chiral fluoro-pharmaceuticals, which account for 18% of all fluoro-pharmaceuticals, are less common. Synthetic methodologies for chiral fluorinated drug candidates need further development. The authors conclude that the potential of fluoro-pharmaceuticals is expected to increase with advancements in fluorine chemistry and synthetic methods, particularly in the synthesis of fluorinated heterocyclic compounds. They emphasize the importance of continued research in this area to enhance the development of novel fluoro-pharmaceuticals.