The ability to noninvasively map, monitor, and manipulate the activity of millions of neurons at single cell and millisecond resolution is hindered by the turbid and light scattering nature of living nervous tissue. Two-photon microscopy permits visualization of single neurons only at a depth of 1 mm, and functional magnetic resonance imaging provides only an indirect means to measure the gross activity of ensembles of neurons. In the awake behaving animal invasive fiber optic probes are required to visualize and manipulate circuits at the single cell level at depths greater than 1 mm. These probes have a limited depth of field and width of view. New technologies are needed to overcome these obstacles to advance brain research and develop new methods for diagnosing and treating brain diseases such as Alzheimer’s disease, schizophrenia, depression, and substance abuse.