Large-scale cancer genomics, proteomics and RNA-sequencing efforts are currently mapping in fine detail the genetic and biochemical alterations that occur in cancer. However, it is becoming clear that it is difficult to integrate and interpret these data and to translate them into treatments. This difficulty is compounded by the recognition that cancer cells evolve, and that initiation, progression and metastasis are influenced by a wide variety of factors. To help tackle this challenge, the US National Cancer Institute Physical Sciences-Oncology Centers initiative is bringing together physicists, cancer biologists, chemists, mathematicians and engineers. How are we beginning to address cancer from the perspective of the physical sciences?