Reactions for the controlled, catalytic formation of carbon-carbon bonds are crucial for modern organic synthesis. In an idealized sense, they enable a rapid, convergent assembly of molecular complexity. Among such transformations, the formation of C–C bonds at Csp3-hybridized centers is a particularly desirable construct because of its potential to provide access to 3D-rich architectures and, akin to the Suzuki sp2-sp2 coupling, impact the way that novel chemical space is accessed. Toward this goal, metallaphotoredox catalysis has been enlisted as a valuable advance to forge Csp3–Csp2 linkages through single-electron-transfer (SET) under mild reaction conditions. Recent research efforts have broadened the scope of radical progenitors from feedstock chemicals including aliphatic carboxylic acids, aldehydes, bromides, and organosilanes. In subsequent studies, a photochemical/Ni-mediated decarboxylative strategy is accomplished through electron donor-acceptor (EDA) complex activation bypassing the need for stoichiometric metal reductants or exogenous photocatalysts. To facilitate sequential bond formation, net-neutral radical/polar crossover is utilized to achieve the 1,2-dicarbofunctionalization of olefins with organotrifluoroborate nucleophiles. Among the applications in which the ability to accommodate diverse reaction modalities and molecular complexity becomes critical is DNA-Encoded Library (DEL) synthesis. Recently, DEL technology has emerged as an innovative screening modality for the discovery of therapeutic candidates in the pharmaceutical industry. The platform enables a cost-effective, time-efficient, and large-scale assembly and interrogation of billions of small organic ligands against a biological target in a single experiment. To increase chemical diversity, the implementation of photoredox catalysis in DELs, including Ni-catalyzed manifolds and radical/polar crossover, has enabled the construction of novel structural scaffolds. To expand chemical space, a decarboxylative-based hydroalkylation of DNA-conjugated trifluoromethyl-substituted alkenes driven by SET and subsequent hydrogen atom termination through EDA complex activation is detailed. In a further protocol, the coupling of electronically unbiased olefins is achieved through the intermediacy of (hetero)aryl radical species with full retention of the DNA tag integrity. In summary, photoredox catalysis offers new avenues for unique synthetic disconnections toward bioactive molecules. The diverse nature of amenable radical precursors, combined with the mild and modular character of photochemical paradigms, facilitate the generation of chemotypes that possess a high density of pendant functional groups.