Transition metal-catalyzed carbon-heteroatom bond formation is fundamental to modern synthetic organic chemistry, playing a pivotal role in the synthesis of pharmaceuticals, agrochemicals, and materials. These transformations are typically performed using palladium (Pd), 1,7-13 copper (Cu), or nickel (Ni) precatalysts, with their efficiency reliant on the precise balance of ligands, solvents, and bases for the key catalytic steps to effectively occur. Despite substantial progress, achieving the optimal synergy between ligands and bases remains especially challenging, often requiring case-by-case optimization. While effective ligand design is essential for optimizing oxidative addition, reductive elimination, and active catalyst formation and stability, base selection influences nucleophile binding, deprotonation, and overall catalyst performance. Traditional methods often rely on inorganic bases or strong anionic bases with low nucleophilicity. However, these bases present several challenges, such as insolubility in organic solvents, dependence on particle size and stirring speed on reaction efficiency, the need for elevated temperatures, and clogging during continuous flow up-scaling. Strong anionic bases suffer from moisture sensitivity and limited compatibility with electrophilic functional groups. In response to these challenges, there has been increasing interest in utilizing organic bases, such as guanidines, amidines, and phosphazenes. Although these bases are more expensive, they offer solubility advantages and, in some cases, improved functional group tolerance. Nonetheless, the field remains dependent on the development of specific ligands and the optimization of conditions for each reaction. For example, Stradiotto and co-workers developed the first thermal protocol for C(sp²)-O crosscoupling reactions using organic bases in combination with the PAd2-DalPhos as a ligand. The interplay between ligand and base is underscored by the success of coupling aliphatic alcohols with DBU, whereas BTPP is required for reactions with phenols. Milder and more cost-effective alkyl amines present a promising alternative but often lack sufficient basicity for effective deprotonation. To tackle this, Buchwald and co-workers elegantly designed an electron-deficient ligand that allows the deprotonation of nickel-bound anilines with triethylamine for cross-coupling with aryl triflates. Notably, using the more nucleophilic base, DBU, inhibits the reaction due to its preferential coordination to nickel, demonstrating the additional layer of complexity in achieving the optimal balance between ligands and bases when working with weakly nucleophilic coupling partners. Similarly, recent advances in catalytic electrochemical and photochemical methods also allowed the use of soluble organic bases. For instance, Baran and co-workers reported an efficient electrochemical nickel-catalyzed cross-coupling of aliphatic alcohols using a bipyridine ligand and DBU, although this method was ineffective for aromatic alcohols. Johannes