In this study, we investigate the effect of substituents in determining the modes of one-electron reductive cleavage of X–NRR′ (X = Cl and Br) molecules. We achieve this through comparison of the calculated gas-phase electron affinities (EAs) and aqueous-phase one-electron reduction potentials (E°’s) for a range of nitrogen-centered radicals (•NRR′) with the corresponding EA and E° values for •Cl and •Br. The gas-phase EAs have been obtained using the benchmark-quality W1w thermochemical protocol, whereas E° values have been obtained by additionally applying free energy of solvation corrections, obtained using the conductor-like polarizable continuum (CPCM) model. We find that the N-halogenated derivatives of amines and amides should generally cleave in such a way as to afford •NRR′ and X–. For the N-halogenated imides, on the other hand, the N-brominated derivatives are predicted to produce •Br in solution, whereas the N-chlorinated derivatives again would give Cl–. Importantly, we predict that N-bromouracil is likely to afford •Br. This may have important implications in terms of inflammatory-related diseases, because •Br may damage biomolecules such as proteins and DNA. To assist in the determination of the gas-phase EAs of larger •NRR′ radicals, not amenable to investigation using W1w, we have evaluated the performance of a wide range of lower-cost theoretical methods. Of the standard density functional theory (DFT) procedures, M06-2X, τ-HCTHh, and B3-LYP show good performance, with mean absolute deviations (MADs) from W1w of 4.8–6.8 kJ mol–1, whereas ROB2-PLYP and B2-PLYP emerge as the best of the double-hybrid DFTs (DHDFTs), with MADs of 2.5 and 3.0 kJ mol–1, respectively. Of the Gn-type procedures, G3X and G4 show very good performance (MADs = 2.4 and 2.6 kJ mol–1, respectively). The G4(MP2)-6X+ procedure performs comparably, with an MAD of 2.7 kJ mol–1, with the added advantage of significantly reduced computational expense.