Cell Systems was established in 2015 to provide a home at Cell Press for elegant work that addresses fundamental questions in systems biology. "Systems biology," as we broadly define it, is work that develops a rigorous understanding of any biological phenomenon where one plus one does not apparently equal two. Disciplines in the physical sciences have met this challenge for a long time, and we've found that our strongest papers tend to apply classic approaches taken in physics, engineering, mathematics, and computer science to salient biological questions. Manuscripts describing discoveries, milestone achievements, broadly useful tools or resources, or insights into the use of technology may all be appropriate. Cross-disciplinary studies that reveal general principles of systems are particularly welcome