In this Highlight the most important approaches in CSP to tackle molecular flexibility are characterized. Their successful use for drug-like molecules emphasizes the maturity of zeroth order CSP, while limitations indicate places for improvement.

We apply a unique sequence of structural and dynamical neutron-scattering techniques, augmented with density-functional electronic-structure calculations, to establish the degree of polymorphism in an archetypal hydrogen-bonded system – crystalline formic acid. Using this combination of experimental and theoretical techniques, the hypothesis by Zelsmann on the coexistence of the β₁ and β₂ phases above 220 K is tested. Contrary to the postulated scenario of proton-transfer-driven phase coexistence, the emerging picture is one of a quantitatively different structural change over this temperature range, whereby the loosening of crystal packing promotes temperature-induced shearing of the hydrogen-bonded chains. The presented work, therefore, solves a fifty-year-old puzzle and provides a suitable framework for the use neutron-Compton-scattering techniques in the exploration of phase polymorphism in condensed matter.