Since its coming of age in the mid 1960s, continuum biomechanics has contributed much to our understanding of human health as well as to disease, injury, and their treatment. Nevertheless, biomechanics has yet to reach its full potential as a consistent contributor to the improvement of health–care delivery. Because of the inherent complexities of the microstructure and biomechanical behaviour of biological cells and tissues, there is a need for new theoretical frameworks to guide the design and interpretation of new classes of experiments. Because of continued advances in experimental technology, and the associated rapid increase in information on molecular and cellular contributions to behaviour at tissue and organ levels, there is a pressing need for mathematical models to synthesize and predict observations across multiple length– and time–scales. And because of the complex geometries and loading conditions, there is a need for new computational approaches to solve the boundaryand initial–value problems of clinical, industrial, and academic importance. Clearly, much remains to be done. The purpose of this paper is twofold: to review a few of the many achievements in the biomechanics of soft tissues and the tools that allowed them, but, more importantly, to identify some of the open problems that merit increased attention from those in applied mechanics, biomechanics, mathematics and mechanobiology.