The first SciBX Summit on Innovation in Drug Discovery & Development, held in Boston in September, addressed the opportunity afforded by macrocycles and constrained peptides to open up vast new therapeutic target space, the underlying basic science unknowns that are impeding progress and potential paths to systematically unlocking the promise of macrocycle-based medicines. At the macrocycle summit, participants identified four areas of science in which work is needed to enable innovation. After identifying the translational hurdles, the group identified action items that could catalyze progress across the various macrocycle platforms.