Upon activation by extracellular stimuli, G protein-coupled receptors (GPCRs) activate complex intracellular signaling networks to invoke diverse cellular responses that ultimately culminate in changes to protein expression levels. Historically, standard practice for global evaluation of the downstream consequences of GPCR signaling relies on measuring RNA expression rather than protein expression. However, we know that transcription is not the end-game for cells, and there is substantial evidence in a broad array of contexts indicating that these two expression levels are often uncorrelated. I set out to address this issue and explore the consequences of post-transcriptional regulation of cellular responses to GPCR activation. Previous work from the Tsvetanova lab has described a fluorescent reporter for assessing cAMP-induced gene expression. I extended this platform to directly compare mRNA and protein expression and employed it in parallel with a luciferase cAMP reporter to systematically evaluate a panel of agonists targeting Gαs-coupled receptors. These data demonstrated a non-linear relationship between agonist-induced cAMP levels, mRNA expression, and protein expression, even for ligands of the same receptor. To evaluate this phenomenon on a global scale under endogenous conditions, I paired traditional RNA sequencing with ribosome profiling, a next-generation sequencing-based technique that preferentially captures ribosome-occupied mRNA to generate a snapshot view of active translation. Using this strategy to approximate agonist-induced changes in protein expression decoupled from changes in mRNA expression, I identified 30+ exclusively post-transcriptionally regulated downstream targets of GPCR activation. With these data as the basis of an integrative multi-omics analysis, I am building a comprehensive picture of post-transcriptional control of cellular responses to receptor activation. This study demonstrates the potential applications for unbiased methods to dissect the downstream consequences of receptor function and identify novel potential regulators of GPCR signaling.