This review covers the enantioselective lithiation–substitution at the α-position of nitrogen-containing heterocycles mediated by strong organolithium bases and chiral ligands. The reactions occur by two main mechanistic pathways: asymmetric deprotonation and asymmetric substitution. For N-Boc heterocycles, asymmetric deprotonation is the predominant pathway, and s-BuLi, in combination with chiral diamines, such as (–)-sparteine and the (+)-sparteine surrogate, are used. This approach is highly successful with N-Boc pyrrolidines, piperidines, and piperazines. Substrates for asymmetric-substitution-mediated reactions include some N-Boc heterocycles, but other N-substituents, such as N-alkyl groups, N-alkyl-BY3 salts (Y = H, F) and N-thioamide groups are also used. With both mechanistic pathways, the lithiated heterocycle can be transmetalated to form an organocopper or organozinc species to widen the scope of the electrophile. The full scope and limitations of this approach to synthesize enantioenriched α-substituted aziridines, azetidines, pyrrolidines, piperidines, piperazines, azepanes and other five-/six-membered-ring heterocyles are summarized.