Heavy metals such as lead, chromium, mercury, and bismuth are being utilized in various processes such as industrial preparation, mining, batteries, being a part of vehicular exhaust, agricultural waste is polluting the environment. Hence, their detection and removal is a big concern in the research area. On the other hand, toxic volatile organic carbons (VOCs) also pose serious threats to human life as they are present in air. In this book chapter, we have discussed Cyclodextrins and the role of their host–guest chemistry in sensing toxic heavy metal ions and VOCs. Cyclodextrins are macrocyclic molecules having a unique structure comprising of glucopyranose molecules attached through alpha-1, 4 glycosidic linkages in a cyclic or ring form resulting in a helical shape. Cyclodextrin-based rigid ring or cavity can act as a host for the analyte and it exhibits host–guest chemistry through a coordination mechanism. They are highly efficient, biocompatible, water soluble, cost effective, and easily available. Metal ions can form chelates or complexes with the suitable functional groups present inside the moiety. As a result, the metal ion is encapsulated inside and there is an increase (Turn on chemosensor) or decrease (Turn off chemosensor) in the luminescence properties of the host cyclodextrin moieties. Similarly, VOCs can also interact with the hydrophobic cavity of cyclodextrins. It forms the basis of sensing and is studied through spectrofluorometric systems. The main feature of fluorescence sensing is selectivity w.r.t. different analytes which plays a pivotal role. Sensitivity towards the specific analyte, mechanism of interaction, and medium of coordination are the other key features of the sensing mechanism. Sensing can be observed with or without a blue/red shift. Nowadays, researchers are also working on modified cyclodextrins which is also a part of the given chapter. Hence, it’s a vast area of research and currently in demand.