In this critical review, the strategic and economic benefits of C-H functionalization logic will be analyzed through the critical lens of total synthesis. In order to illustrate the dramatically simplifying effects this type of logic can potentially have on synthetic planning, we take the reader through a series of case studies in which it has already been successfully applied. In the first section, a chronological look at key historical syntheses will be examined, leading into modern day examples. In the second section, our own experience with applying and executing synthesis with a C-H functionalization "mindset" will be discussed (114 references).