Nanoparticles exist far from the equilibrium state due to their high surface energy. Nanoparticles are therefore extremely unstable and easily change themselves or react with active substances to reach a relatively stable state in some cases. This causes desired changes or undesired changes to nanoparticles and thus makes them exhibit a high reactivity and a poor stability. Such dual nature (poor stability and high reactivity) of nanoparticles may result in both negative and positive effects for nanoparticle processing. However, the existing studies mainly focus on the high reactivity of nanoparticles, whereas their poor stability has been neglected or considered inconsequential. In fact, in some cases the unstable process, which is derived from the poor stability of nanoparticles, offers an opportunity to design and fabricate unique nanomaterials, such as by chemically transforming the “captured” intermediate nanostructures during a changing process, assembling destabilized nanoparticles into larger ordered assemblies, or shrinking/processing pristine materials into the desired size or shape via selective etching. In this review, we aim to present the stability and reactivity of nanoparticles on three levels: the foundation, concrete manifestations, and applications. We start with a brief introduction of dangling bonds and the surface chemistry of nanoparticles. Then, concrete manifestations of the poor stability and high reactivity of nanoparticles are presented from four perspectives: dispersion stability, thermal stability, structural stability, and chemical stability/reactivity. Next, we discuss some issues regarding the stability and reactivity of nanomaterials during applications. Finally, conclusions and perspectives on this field are presented.