Depending on the choice of the reagent, 2‐(trifluoromethyl)pyridine can be selectively metalated and subsequently carboxylated or otherwise functionalized either at the 3‐ or at the 6‐position. “Optional site selectivity” can also be achieved with 4‐(trifluoromethyl)pyridine, which may be deprotonated either at the 2‐ or at the 3‐position. In contrast, 3‐(trifluoromethyl)pyridine undergoes nucleophilic addition and ensuing decomposition whatever the base. Depending on the reaction conditions, 2‐(trifluoromethyl)quinoline displays reactivity toward lithium reagents at its 3‐, 4‐, or 8‐positions, 3‐(trifluoromethyl)quinolines at the 2‐ or 4‐positions, and 4‐(trifluoromethyl)quinoline at the 2‐ or 3‐positions. It was therefore possible to prepare four trifluoromethyl‐substituted pyridinecarboxylic acids (1, 4, 9, and 10) and six trifluoromethyl‐substituted quinolinecarboxylic acids (11, 13, 14, 15, 17, and 18) regioisomerically uncontaminated and in a most straightforward way. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)