RNA folding is the most essential process underlying RNA function. While significant progress has been made in understanding the forces driving RNA folding in vitro, exploring the rules governing intracellular RNA structure formation is still in its infancy. The cellular environment hosts a great diversity of factors that potentially influence RNA folding in vivo. For example, the nature of transcription and translation is known to shape the folding landscape of RNA molecules. Trans-acting factors such as proteins, RNAs and metabolites, among others, are also able to modulate the structure and thus the fate of an RNA. Here we summarize the ongoing efforts to uncover how RNA folds in living cells.