CASE (computer‐assisted structure elucidation) first appeared in the late 1960s but really gained traction in the 1990s as more information‐rich 2D NMR experiments were developed. In this article, we discuss the strategies of CASE for small organic molecules in solution. Cognitive grounds and the principal CASE flow‐diagram, as well as the main obstacles impeding structure elucidation (presence of ‘nonstandard’ correlations and ambiguity of 2D NMR data, deficit of hydrogen, etc.) are discussed and methods to overcome these challenges are suggested. The methods are illustrated by examples of solving challenging problems. It has been shown that CASE can be used to avoid pitfalls during structure elucidation and to determine the most efficient combinations of 2D NMR experiments. Methodology of DFT‐based NMR spectrum prediction in synergistic combination with CASE is explained. The last advances in 3D structure elucidation and stereochemistry determination using RDCs and RCSAs are considered. In conclusions, perspectives of CASE development are discussed.