RNA helicases are members of a large family of enzymes that function in unwinding RNA duplexes and modulating interactions between RNAs and proteins. RNA helicases participate in numerous cellular processes, including transcription, translation, mRNA export, nonsense-mediated mRNA decay, and telomere maintenance. In this review, we discuss the recent discoveries on several RNA helicases that play key roles in aging and lifespan regulation. We first describe the roles of several mammalian RNA helicases implicated in cellular senescence. In addition, we discuss our previous reports showing that three RNA helicases, HEL-1/DDX39, SACY-1/DDX41 and SMG-2/UPF1, promote longevity in Caenorhabditis elegans through distinct mechanisms. These findings reveal the critical functions of many RNA helicases in regulating aging and may lead to insights into the importance of RNA homeostasis in aging and longevity.