The last 30 years have seen tremendous advances in creating patient-specific mathematical and computational models to aid in the diagnosis and treatment of human diseases. This has been driven by advances in computational mechanics as well as high performance computing, medical imaging and artificial intelligence. The sophistication of computational models and physiologic realism is remarkable. Furthermore, in the last decade there has been great progress in applying these models in pharmaceutical and medical device design as well as direct clinical application with software-enabled clinical services based on computational mechanics models. This minisymposium is focused on the development of mathematical and computational methods for biomedical digital twins with an emphasis on comprehensive models of human physiology and clinical applications.