The discovery of catalytic RNA (ribozymes) more than 30 years ago significantly widened the horizon of RNA‐based functions in natural systems. Similarly to the activity of protein enzymes that are often modulated by the presence of an interaction partner, some examples of naturally occurring ribozymes are influenced by ligands that can either act as cofactors or allosteric modulators. Recent discoveries of new and widespread ribozyme motifs in many different genetic contexts point toward the existence of further ligand‐dependent RNA catalysts. In addition to the presence of ligand‐dependent ribozymes in nature, researchers have engineered ligand dependency into natural and artificial ribozymes. Because RNA functions can often be assembled in a truly modular way, many different systems have been obtained utilizing different ligand‐sensing domains and ribozyme activities in diverse applications. We summarize the occurrence of ligand‐dependent ribozymes in nature and the many examples realized by researchers that engineered ligand‐dependent catalytic RNA motifs. We will also highlight methods for obtaining ligand dependency as well as discuss the many interesting applications of ligand‐controlled catalytic RNAs. WIREs RNA 2017, 8:e1395. doi: 10.1002/wrna.1395This article is categorized under: RNA-Based Catalysis > RNA–Mediated Cleavage RNA-Based Catalysis > Miscellaneous RNA–Catalyzed Reactions Regulatory RNAs/RNAi/Riboswitches > Riboswitches