Cells employ highly dynamic signaling networks to drive biological decision processes. Perturbations to these signaling networks may attract cells to new malignant signaling and phenotypic states, termed cancer network attractors, that result in cancer development. As different cancer cells reach these malignant states by accumulating different molecular alterations, uncovering these mechanisms represents a grand challenge in cancer biology. Addressing this challenge will require new systems-based strategies that capture the intrinsic properties of cancer signaling networks and provide deeper understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies.