Viewing long-standing questions and challenges through a different lens can often provide unique insights and perspectives. This has been the key to many of the innovations emerging in the field of optical microscopy. Whether one is devising novel superresolution localization microscopies (1), new imaging reagents (2,3), or exploiting new imaging modalities to study challenging cellular structures and processes (4,5), the key driver remains acquiring quantitative insights into structure, dynamics, and ultimately functionality.