In this review, transformations of C-F to C-X bonds mediated by transition-metal complexes are considered from the ligand’s perspective. In C-F bond activation reactions, the ligands (L) bonded to transition-metal complexes can act as spectators but can also assist the reaction. The latter case is important in the heterolytic cleavage of C-F bonds by nucleophilic addition reactions. When L is an electrophile (E), the assistance of the ligand facilitates the fluoride departure when the metal attacks at C. In contrast, when L is a nucleophile (X), the ligand is responsible for the nucleophilic addition and the reaction leads to a new C-X bond, allowing the direct functionalization of C-F bonds. This article presents an overview of the reactions that are initiated by the nucleophilic attack of a coordinated ligand (a hydride or an N-, O-, or S-nucleophile) to a CF carbon resulting in formation of a new C-H, C-N, C-O, or C-S bond. The possible mechanisms are discussed. The attack of a nucleophilic ligand at the electrophilic carbon of a C-F bond is comparable to fluoride elimination by organic nucleophiles. However, the presence of the metal center introduces new features in this process, both in the selectivity and in the thermodynamics. Herein these effects are analyzed. Thus, the aim of this review is to show how these kinds of processes put together the best of both organic and inorganic worlds in order to achieve a wide range of reactions with fluorinated compounds.