Systems Biology refers to the integration into biology of ideas and methodologies from mathematics, engineering, computer science, physics, and chemistry, with the goal of deriving greater understanding from data—especially data that are complex, dynamic and/or high-dimensional. Systems biology makes frequent use of explicit, quantitative models, and concerns itself both with how useful models can be derived from data as well as how models can be used to generate hypotheses and drive the collection of new data. Modern biological and biomedical research are becoming increasing reliant on systems biology approaches, yet because the skills and insights necessary to implement such approaches come from so many different disciplines, it can be challenging for researchers to take full advantage of them. The goal of the Systems Biology Core is to enable skin biology researchers to incorporate systems biology in their research, thereby enhancing productivity and increasing research impact. The core will help skin biologists derive more meaningful models from data; build and analyze explicit, quantitative models; use models to interpret, analyze, and integrate data (including data generated by other cores); use models to generate and prioritize testable hypotheses about function; and better understand and utilize literature that draws upon systems biology ideas and approaches. Methodologies to be made available through the Systems Biology Core are especially well suited to building upon data from, and providing input into, the efforts of the imaging and genomics/bioinformatics cores. Strategies for achieving these goals include targeted workshops for skin biologists, inclusion of skin biologists in an annual systems biology retreat, systems biology “clinics” at which skin biologists identify problems in need of attention, and individualized consultation. These strategies leverage the expertise and resources of three systems biology faculty with expertise in modeling and data analysis; long-standing experience in teaching interdisciplinary science; and a track-record of collaboration with skin biologists. It also leverages the infrastructure of a large campus-wide center devoted to systems biology, the Center for Complex Biological Systems.