Several different ways to predict RNA secondary structures have been suggested in the literature. Statistical methods, such as those that utilize stochastic context-free grammars (SCFGs), or approaches based on machine learning aim to predict the best representative structure for the underlying ensemble of possible conformations. Their parameters have therefore been trained on larger subsets of well-curated, known secondary structures. Physics-based methods, on the other hand, usually refrain from using optimized parameters. They model secondary structures from loops as individual building blocks which have been assigned a physical property instead: the free energy of the respective loop. Such free energies are either derived from experiments or from mathematical modeling. This rigorous use of physical properties then allows for the application of statistical mechanics to describe the entire state space of RNA secondary structures in terms of equilibrium probabilities. On that basis, and by using efficient algorithms, many more descriptors of the conformational state space of RNA molecules can be derived to investigate and explain the many functions of RNA molecules. Moreover, compared to other methods, physics-based models allow for a much easier extension with other properties that can be measured experimentally. For instance, small molecules or proteins can bind to an RNA and their binding affinity can be assessed experimentally. Under certain conditions, existing RNA secondary structure prediction tools can be used to model this RNA-ligand binding and to eventually shed light on its impact on structure formation and function.