This review addresses the question: ‘When can optimizing the physical form rescue leads with poor drug-like properties.’ This review addresses strategies involving: (1) alternate polymorphs or solvates; (2) salts; and (3) cocrystals. Amorphous materials are also briefly addressed. Overall, it is clear, based upon the unique properties that a new form can provide that optimizing the solid form can rescue a drug lead. What is not known or predictable is when an optimized form will be found or occur. Instead, one must screen to try to find a ‘home run’ form.