Molecular crystals are prevalent across a diverse range of materials applications, including opto-electronics, pharmaceuticals, and energetic materials. The desirable properties of these materials are often strongly tied to the crystal structure-the arrangement of the molecules in the crystal lattice-and changes solely in the crystal structure can greatly affect a wide range of the physio-chemical properties of the crystals. This is seen clearly in polymorphs, which are crystals of the same compound but with different crystal structures. The properties of polymorphs often differ substantially, such that the unexpected appearance of a polymorph can result in loss of control over material properties; the example of polymorphism in the drug Ritonavir illustrates the impact that this can have in pharmaceutical materi-als. Polymorphs also offer an opportunity since they allow for materials to be potentially tuned to achieve enhanced properties. Thus, predicting the crystal structure of molecular crystals has become a highly coveted goal and crystal structure prediction (CSP) is one of the primary challenges in materials science and computational chemistry.