RNA-protein interactions play a critical role in post-transcriptional gene regulation. Characterizing these interactions in their native context has been challenging; however, advances in RNA sequencing and mass spectrometrybased proteomics combined with innovative chemical biological tools have heralded the development of robust strategies for performing biochemistry on a cellular scale. Herein, we review recent advances in the development and application of proteomic and transcriptomic approaches to profile cellular RNA-protein interactions, focusing on sequencing-based strategies and proteomic analysis of RNA-binding proteins, as well as approaches to address the role of RNA modifications in protein-RNA binding events.