Lithium diisopropylamide (LDA) plays an integral role in organic synthesis. In a comprehensive survey of over 500 total syntheses conducted by Reich, LDA emerged as the most commonly used reagent attesting to its broad range of synthetic applications. Its widespread utility led Collum to investigate mechanisms of LDA-mediated lithiation; a survey of these studies was assembled into a review that paints a coherent picture of generalized LDA-mediated reactions conducted at or above -40 °C. Fast LDA aggregate exchange inherent at high temperatures precludes detailed mechanistic understanding of aggregation dynamics by rendering substrate lithiation rate-limiting. By lowering the temperature to -78 °C, the rate of aggregate exchange can become comparable to the rate of metalation in THF. Time dependent decays exhibit linear and sigmoidal curvatures under pseudo-first order conditions, foreshadowing mechanistic complexity. Under this non-limiting regime, aggregates are no longer in full equilibrium, causing the reaction to become sensitive to autocatalysis, exogenous salts, and trace impurities. Subtle changes to reaction conditions, including isotopic substitution, can shift the rate-limiting step unpredictably. The work described herein presents two experimental accounts for elucidating mechanisms of lithiation: ortholithiation of 1,4-difluorobenzene and ortholithiation of 1,4-bis(trifluoromethyl)benzene. Given the highly substrate-dependent mechanisms, both substrates present different views of LDA deaggregation with internal consistency. i The third experimental account presents a fruitful collaboration with Zakarian aimed at understanding the underlying chemical basis for enantioselective alkylations of the enediolate of phenylacetic acid in the presence of a lithiated C2-symmetric tetraamine ligand. The high facial selectivity was traced to the formation of a densely functionalized mixed aggregate. ii