Pharmaceutical cocrystals have gained increased attention at least in part because of their potential for enhancing physicochemical and biopharmaceutical properties of existing drugs. As a result, design, screening, and large-scale preparation of pharmaceutical cocrystals have been emphasized in recent research. The design of pharmaceutical cocrystals has focused primarily on determining the empirical guidelines regarding the hierarchy of supramolecular synthons. However, this approach is typically less predictive when considering drugs that are complex in nature, such as those having a multiplicity of functional groups and/or numerous degrees of conformational flexibility. In this manuscript, we report a crystal engineering design strategy to facilitate the synthesis of multicomponent crystal forms of the atypical antipsychotic drug olanzapine, marketed as a drug product under the trade name Zyprexa. Comprehensive analysis and data mining of existing crystal structures of olanzapine were followed by grouping into categories according to the crystal packing exhibited and systematically using this information to crystal engineer new compositions. This approach afforded isostructural, quaternary multicomponent crystal forms of olanzapine composed of a stoichiometric ratio of four molecular components: olanzapine; a cocrystal former; water; solvent (isopropylacetate). To our knowledge this study is unprecedented in that the observed quaternary structures can be classified as solvates, hydrates, or cocrystals.