RNA folds to a myriad of three-dimensional structures and performs an equally diverse set of functions. The ability of RNA to fold and function in vivo is all the more remarkable because, in vitro, RNA has been shown to have a strong propensity to adopt misfolded, non-functional conformations. A principal factor underlying the dominance of RNA misfolding is that local RNA structure can be quite stable even in the absence of enforcing global tertiary structure. This property allows non-native structure to persist, and it also allows native structure to form and stabilize non-native contacts or non-native topology. In recent years it has become clear that one of the central reasons for the apparent disconnect between the capabilities of RNA in vivo and its in vitro folding properties is the presence of RNA chaperones, which facilitate conformational transitions of RNA and therefore mitigate the deleterious effects of RNA misfolding. Over the past two decades, it has been demonstrated that several classes of non-specific RNA binding proteins possess profound RNA chaperone activity in vitro and when overexpressed in vivo, and at least some of these proteins appear to function as chaperones in vivo. More recently, it has been shown that certain DExD/H-box proteins function as general chaperones to facilitate folding of group I and group II introns. These proteins are RNA-dependent ATPases and have RNA helicase activity, and are proposed to function by using energy from ATP binding and hydrolysis to disrupt RNA structure and/or to displace proteins from RNA-protein complexes. This review outlines experimental studies that have led to our current understanding of the range of misfolded RNA structures, the physical origins of RNA misfolding, and the functions and mechanisms of putative RNA chaperone proteins.