Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism ensuring the fast decay of mRNAs harboring a premature termination codon (PTC). As a quality control mechanism, NMD distinguishes PTCs from normal termination codons in order to degrade PTC-carrying mRNAs only. For this, NMD is connected to various other cell processes which regulate or activate it under specific cell conditions or in response to mutations, mis-regulations, stresses, or particular cell programs. These cell processes and their connections with NMD are the focus of this review, which aims both to illustrate the complexity of the NMD mechanism and its regulation and to highlight the cellular consequences of NMD inhibition.