Metal ions are necessary for folding and function of catalytic RNA molecules. However, the structural and mechanistic roles of these ions are poorly understood. For living systems, it is usually assumed that Na(I) and Mg(II) ions are the sole metallic cofactors involved with nucleic acids, both being most abundant and freely available in the cell. However, in living organisms, a multitude of other metal ions is present, although tightly regulated. Furthermore, in biochemical experiments many different metal ions are applied. The recognition of specific metal ions by nucleic acids is very poorly understood as is their effect on structure, folding, and catalytic activity. This study focuses on the thermodynamic and structural characterization of these interactions in large RNAs, i.e. group II intron ribozymes and Mg(II) riboswitches. We are applying a multidisciplinary approach by using a combination of tools from Coordination and Analytical Chemistry as well as Structural Biology. Thus, our results will not only contribute to the understanding of the global structure and function of these naturally occurring RNAs, but they also promise to have a significant impact on the Bioinorganic Chemistry of RNAs and on RNA Biochemistry in general.