The well-known synthetic versatility of metal-organic frameworks (MOFs) is rooted in the ability to predict the metal-ion coordination geometry and the vast possibilities to use organic chemistry to modify the linker groups. However, the use of molecules occupying the pores as a component of framework design has been largely ignored. Recent reports show that the presence of these so-called "guests" can have dramatic effects, even when they are a seemingly innocuous species such as water or polar solvents. We term these guests "non-innocent" when their presence alters the MOF in such a way as to create a new material with properties different from the MOF without the guests. Advantages of using guest molecules to impart new properties to MOFs include the relative ease of introducing new functionalities, the ability to modify the material properties at will by removing the guest or inserting different ones, and avoidance of the difficulties associated with synthesizing new frameworks, which can be challenging even when the basic topology remains constant. In this article, we describe the "Guest@MOF" concept and provide examples illustrating its potential as a new MOF design element.