Research on resting state brain activity using fMRI offers a novel approach for understanding brain organization at the systems level. Resting state fMRI examines spatial synchronization of intrinsic fluctuations in blood-oxygenation-level-dependent (BOLD) signals arising from neuronal and synaptic activity that is present in the absence of overt cognitive information processing. Since the discovery of coherent spontaneous fluctuations within the somatomotor system (Biswal, et al. 1995), a growing number of studies have shown that many of the brain areas engaged during various cognitive tasks also form coherent large-scale brain networks that can be readily identified using resting state fMRI. These studies are beginning to provide new insights into the functional architecture of the human brain. This Research Topic will synthesize current knowledge about resting state brain activity and discuss their implications for understanding brain function and dysfunction from a systems neuroscience perspective. This topic will also provide perspectives on important conceptual and methodological questions that the field needs to address in the next years. In addition to invited reviews and perspectives, we solicit research articles on theoretical, experimental and clinical questions related to the nature, origins and functions of resting state brain activity.