Radiopharmaceutical therapies (RPTs) are gaining increased interest with the recent emergence of novel safe and effective theranostic agents, improving outcomes for thousands of patients. The term theranostics refers to the use of diagnostic and therapeutic agents that share the same molecular target; a major step toward precision medicine, especially for oncologic applications. The authors dissect the fundamentals of theranostics in nuclear medicine. First, they explain the radioactive decay schemes and the characteristics of emitted electromagnetic radiation used for imaging, as well as particles used for therapeutic purposes, followed by the interaction of the different types of radiation with tissue. These concepts directly apply to clinical RPTs and play a major role in the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that can help estimate patient-specific absorbed doses, in tumors as well as normal organs. Dosimetry in RPT is an area of active investigation, as most of what we know about the relationship between delivered dose and tissue damage is extrapolated from external-beam radiation therapy; more research is needed to understand this relationship as it pertains to RPTs. Tumor heterogeneity is increasingly recognized as an important prognostic factor. Novel molecular imaging agents, often in combination with fluorine 18-fluorodeoxyglucose, are crucial for assessment of target expression in the tumor and potential hypermetabolic disease that may lack the molecular target expression. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.