Transition metal catalyzed C—H activation is an extremely important process, both for its fundamental scientific interest and for its potential to produce functionalized hydrocarbons. In order to achieve an effective functionalization, many investigations have been directed toward the understanding of this process. Experimentally, the nature of this step remains challenging as the dividing line between the various mechanistic possibilities can be unclear. The use of computational chemistry has provided more insight into such mechanistic issues. More in-depth mechanistic studies have shown subtleties in previously generalized processes. Therefore, this chapter will highlight the powerful synergy that the combination of experimental and computational study provides toward the understanding of the mechanisms of C—H activation and functionalization.