During the process of developing a synthesis to a complex molecule, multiple decisions are made regarding the strategies and tactics used to prepare key bonds. In this article, we preface a series of papers describing the development of the commercial synthesis of BMS-663068 (a potential new treatment for HIV), with an in-depth discussion of the important strategic decisions made during the process of designing and demonstrating the proposed commercial synthesis of this complex clinical candidate. We discuss the key strategic disconnections and the key experimental data used to drive our tactical decisions during development. In the remaining articles in this series, we outline the development of these enabling chemical processes into scalable procedures ready to support commercialization of this promising new medicine.