The development of sustainable catalytic methods for the selective functionalization of small molecules remains a major challenge in modern chemistry, with wide-ranging impact in synthesis, medicinal chemistry, and environmental remediation. Among the most relevant functionalizations in synthesis is the borylation of small molecules, providing access to organoboronate esters which are versatile intermediates in organic synthesis. Complementarily, the hydrodefluorination (HDF) of small molecules renders access to partially fluorinated synthons and serves as a model for deuterodefluorination (DDF), enabling site-selective deuterium incorporation for ADME studies and the synthesis of deuterated drugs. Beyond synthesis, HDF is also a key strategy for the degradation of persistent fluorinated compounds (PFAs), offering important environmental applications. In this talk, I will present fundamentally novel and sustainable catalytic strategies developed in our laboratory for borylation and hydro-/deuterodefluorination processes. These include the discovery of highly efficient and broadly applicable homogeneous systems for C–H borylation and single or sequential hydroboration reactions, including manganese catalysts and the unexpected catalytic activity of HSi(OEt)₃. In parallel, we have designed Fe and Ni catalysts for the selective HDF and DDF of C(sp²)–F bonds and CF₃ groups in arenes and pyridines, establishing a new platform for sustainable and broadly impactful transformations. Collectively, these results provide significant advances with wide-reaching implications across fundamental catalysis, synthetic methodology, medicinal chemistry, and environmental remediation, demonstrating how mechanistic insight and substrate-controlled reactivity can be leveraged to guide the design of next-generation sustainable catalysts.