Stress granules (SGs) are cytoplasmic ribonucleoprotein granules that commonly nucleate from the interaction of translationally stalled mRNAs and RNA binding proteins. SGs are involved in the cellular adaptation to stress conditions participating in the regulation of gene expression and cell signaling. While dysregulation of SG dynamics has been increasingly implicated in human disease, a comprehensive understanding of SG composition, particularly of the RNA component, across various conditions remains elusive. Here, we review physiological and pathological aspects of SGs, discuss current and future experimental strategies to identify SG components, and provide insights into the SG RNA world through the meta-analysis of 26 human SG transcriptome datasets.