Over the past few decades, direct functionalization/activation of the C–H bond to C–E (E = C, N, O, S, metal, etc.) bonds has become one of the most valuable and straightforward protocols in modern synthetic chemistry. In parallel, controlling the selectivity remains a central challenge in the catalytic functionalization/activation of C–H bond(s) owing to the subtle differences in the reactivity of the various C–H bonds within the molecule. In this chapter, we discuss the crucial role of noncovalent interactions in C–H bond functionalization in alkanes, alkenes, alkynes, aromatics, heterocyclics, aldehydes and ketones. These weak forces can be powerful tools in the formation/stabilization of intermediates and in controlling the selectivity and outcome of a reaction.