Total-body PET scans will initiate a new era for the PET clinic. The benefits of 40-fold effective sensitivity improvement provide new capabilities to image with lower radiation dose, perform delayed imaging, and achieve improved temporal resolution. These technical features are detailed in the first of this 2-part series. In this part, the clinical impacts of the novel features of total-body PET scans are further explored. Applications of total-body PET scans focus on the real-time interrogation of systemic disease manifestations in a variety of practical clinical contexts. Total-body PET scans make clinical systems biology imaging a reality.