After the first seed concept introduced in the 18th century, different disciplines have attributed different names to dual-functional molecules depending on their application, including bioconjugates, bifunctional compounds, multi targeting molecules, chimeras, hybrids, engineered compounds. However, these engineered constructs share a general structure: a first component which targets a specific cell and a second component that exerts the pharmacological activity. A stable or cleavable linker connects the two modules of a chimera. Herein, we discuss the recent advances in the rapidly expanding field of chimeric molecules leveraging chemical biology concepts. This perspective is focused on bifunctional compounds in which one component is a lead compound or a drug. In details, we discuss chemical features of chimeric molecules, their use for targeted delivery, and for target engagement studies.