Over the past 30 years, structural biology at The Scripps Research Institute (TSRI) has earned a world-class reputation, playing a key role in the growth and development of the institute as a whole. The new Department of Integrative Structural and Computational Biology formally unites the TSRI structural biology faculty with the intent to harness combined structural, biophysical, and computational approaches to tackle the most pressing problems and challenges in the biological and biomedical sciences. Many recent breakthroughs in technologies, methodologies, and accelerated throughput make this an exciting time in structural biology. Additionally, powerful computation and bioinformatics are playing an increasingly important role in all facets of biological research. Thus, the integration of computational methods with the current arsenal of biophysical techniques is central for addressing challenging and complex biological systems. The advent of integrative and hybrid methods is already paying huge dividends where seemingly intractable problems can be approached using a combination of methods. In addition, state-of-the-art technologies are enabling difficult structural targets, like membrane proteins, to be solved. Important membrane protein drug targets, such as GPCRs, which only a few years ago seemed impossible, are now being solved with remarkable regularity. This strong platform is the foundation of the new department that is populated with an illustrious collection of faculty members and their groups versed in cutting-edge biophysical techniques, such as X-ray crystallography, nuclear magnetic resonance (NMR), electron microscopy, and single-molecule studies. The department faculty is currently working in many diverse fields, which include infectious disease, immunology, neurobiology, cell biology, and molecular biology, and on specific areas, such as structure-assisted vaccine design, membrane proteins, enzyme mechanisms, metalloproteins, RNA-protein complexes, DNA repair, protein–ligand docking, and drug discovery. The department is dedicated to research and training in all areas of biophysics, especially as they pertain to the next generation of challenges and opportunities in the biological and biomedical sciences.