This study investigated the anti-apoptotic pathways activated during dehydration and estivation of the African clawed frog, Xenopus laevis. Staying immobile for a significant period of time can cause serious tissue atrophy in non-adapted animals. To preserve skeletal muscle and liver mass, certain metabolic pathways with functions in cell preservation and protection must be activated. This study focused on two families of transcription factors, NF-κB and STAT whose target genes include those with anti-apoptotic functions. The data indicated an upregulation of the NF-ᴋB pathway in liver of dehydrated frogs along with downstream targets Bcl-xL and c-IAP. STAT3 appeared to be active in liver whereas STAT5 was active in skeletal muscle. Relative levels of the NF-κB and STAT downstream target Bcl-2 were elevated in response to dehydration. Analysis of pro- and anti-apoptotic microRNAs indicated that these contribute to post-transcriptional regulation of mRNA transcripts that encode proteins with roles in cell survival.