In this chapter, we review the current understanding of electrophilic aromatic substitution (SEAr) based on the latest experimental and quantum chemical studies. In addition, the most reliable and computationally effective methods for predicting regioselectivity and relative reactivity of SEAr are evaluated and described. The mechanism of nitration is analyzed in detail based on recent quantum chemical studies. In the gas phase, the reaction often has a contribution from a single-electron transfer (SET), and this contribution increases with the activation tendency of the aromatic substrate. The solution reaction lacks a driving force for SET, and the reaction has an early transition state that resembles an O-C coordinated π-complex in structure. In contrast, halogenation with molecular chlorine as the electrophile proceeds via a much later transition state that is more similar to the α-complex. Among the different reactivity descriptors that have been used to analyze regioselectivity and relative reactivity of SEAr, the average local ionization energy seems to have the best predictive power. As is generally the case for descriptor-based approaches, it is best suited for analyzing SEAr with early transition states. The α-complex approach has emerged as an alternative to reactivity descriptors for predicting regioselectivity. It is based on the assumption that the relative α-complex energies are similar to the corresponding transition state energies and thus reflect the positional selectivity for an aromatic substrate when reacting with a particular electrophile. The method provides quantitative predictions for halogenations but is not reliable for nitrations.