Biology is a complex network of molecules that interact, organize, and communicate. We cannot readily visualize most of these species, and yet we are interested in tracking their presence within cells, tissues, or biological fluids in order to provide a deeper understanding of their physiological significance. There has been considerable effort, therefore, to develop chemical sensors that can "see" specific analytes in biological systems.A chemical sensor reports the presence of an analyte by converting a recognition event (usually, but not always, a binding event) into a spectroscopic signal. The analytes of interest include a broad swath of molecule types, including anions, reactive small molecules, proteins, nucleic acids, metal ions, or any other biological or foreign molecule. The spectroscopic signals can be colorimetric, luminescent, magnetic, electrochemical, or radioactive. Currently used sensors largely rely on organic dyes, fluorescent proteins, nanoparticles, and metal complexes for responsive signal transduction. In this chapter, we focus exclusively on the use of metal complexes as design features for chemical sensors. Subsets of this category include radiometals and electroactive metals, which are not covered further here. Instead, we direct interested readers to a recent comprehensive review of the coordination chemistry of radiometals and their application as probes in PET and SPECT imaging [1], as well as reviews on the use of electroactive transition metal receptors for electrochemical sensing applications [2,3].