Recent advances in optical imaging tools for mapping the structural and functional connectomes have greatly augmented our understanding of the brains. The brain is a multilayered and multicompartmental organ where the structures possess multiple length scales, ranging from nanometer (single synapses) to centimeter (whole intact organ), and its functions take place at multiple timescales, ranging from sub-milliseconds (synaptic events) to years (behavioral changes). Therefore, neuroscientists need to image neurocircuits not only at nanometric spatial resolution but also in millisecond time frame in large brain volumes to adequately study neuronal functions. An ideal tool for brain imaging should provide high speed, high resolution, and high contrast with deep penetration in large tissue volumes and sufficient molecular specificity. Toward this end, recent progresses in the optical brain imaging technologies have allowed extracting unprecedented insights into brain. In this chapter, we discuss the various imaging modalities aiming for high-throughput brain imaging, as well as the challenges encountered in imaging the connectome.