Nanomaterials with enzyme-like activities, coined nanozymes, have been researched widely as they offer unparalleled advantages in terms of low cost, superior activity, and high stability. The complex structure and composition of nanozymes has led to extensive investigation of their catalytic sites at an atomic scale, and to an in-depth understanding of the biocatalysis occurring. Single-atom catalysts (SACs), characterized by atomically dispersed active sites, have provided opportunities for mimicking metalloprotease and for bridging the gap between natural enzymes and nanozymes. In this Minireview, we illustrate the unique properties of nanozymes and we discuss recent advances in the synthesis, characterization, and applications of SACs. Subsequently, we outline the impressive progress made in single-atom nanozymes and we discuss their applications in sensing, degradation of organic pollutants, and in therapeutic roles. Finally, we present the major challenges and opportunities remaining for a successful marriage of nanozymes and SACs.