During the last decade ¹⁹F NMR has been developed as a popular tool for biomolecular NMR in living cells. Because there is no background perturbation, high sensitivity or large chemical shift dispersion, this spin-1/2 ¹⁹F nucleus has been selectively incorporated into macrobiomolecules such as proteins and nucleic acids to study their conformation, interactions, and dynamics in a complex cellular environment. This chapter reviews ¹⁹F labeling methods for in-cell NMR and summarizes some of their applications in proteins and nucleic acid studies in cells.