The RNA-binding protein HuR can stabilize and/ or regulate the translation of target mRNAs, thereby affecting the cellular responses to immune, proliferative, and damaging agents. Here, we discuss emerging evidence that HuR elicits a broad anti-apoptotic function through its influence on the expression of multiple target mRNAs. HuR was previously shown to bind to the mRNA encoding the apoptosome inhibitor prothymosin a (ProT alpha) and enhanced its translation and cytoplasmic abundance. More recently, HuR was shown to increase the stability of a target mRNA encoding the pro-survival deacety lase SIRT1. The discovery that HuR likewise binds to and promotes the expression of mRNAs encoding Bcl-2 and Mcl-1, two major anti-apoptotic effectors, strongly supports HuR's role as a key upstream coordinator of a constitutive pro-survival program.