In this chapter, the lead theory of differential leads is presented. A differential lead is an ECG lead obtained from two closely positioned electrodes on the body surface. It can be measured with an ECG body sensor. The theoretical background is needed to gain a formal and intuitive understanding of what is measured with differential leads, as well as to elaborate how the standard 12-lead ECG can be synthesized from three differential leads. The 12-lead ECG synthesis is based on the dipole volume source model. After introducing the dipole model, the Burger’s equation is derived and the concept of lead vector defined. We describe how to derive lead vectors from known heart vector and, vice versa, how to obtain the heart vector from known lead vectors. Then, the concepts of image surface and lead field are introduced, followed with a description of the lead field of a differential lead. Next, the theory and methods for ECG leads synthesis from differential leads is presented. The chapter concludes with a discussion on the evaluation and personalization of the synthesis.