Recent hardware developments focusing on ultra-high field strengths and ultra-high performance gradients from multiple vendors have pushed the limits of achievable spatial resolution for human imaging to the mesoscale (100s of microns) while yielding adequate SNR and exquisite detail and contrast. Leveraging these gains has begun to shed new insight into anatomy, function and composition of tissues. The unprecedented resolution that can now be achieved in vivo has the potential to bridge histology with MRI and address open clinical needs which are unmet at standard resolutions. This plenary aims to provide an overview into how mesoscale imaging can be useful in the clinic, what insights can be derived from the preclinical realm, and how new hardware can be fully exploited with tailored pulse sequence and reconstruction algorithms for in vivo imaging at the mesoscale.