Nucleophilic aromatic substitution (SNAr) reactions are typically used for fluoride introduction into heterocyclic aromatic compounds, but substitution occurs sluggishly with unactivated substrates. This chapter discusses new reagents and methods for fluorination of key heterocyclic pharmacophores. Purines, pyrimidines, pyridines, and even imidazoles are fluorinated readily with anhydrous tetralkylammonium fluorides in DMSO. Though the tetraalkylammonium fluoride reagents themselves are prone to decomposition, the presence of substrate protects these fragile reagents and permits rapid fluorination of relatively reluctant substrates at high temperature. Use of anhydrous fluorinating reagents in radiochemistry is facilitated by a fluoride-relay process that quickly converts hydrated potassium fluoride into anhydrous, exceptionally nucleophilic tetraalkylammonium fluorides.