Recent advances in neuro-technologies have revolutionized knowledge of brain structure and functions. Governments and private organizations worldwide have initiated several large-scale brain connectome projects, to further understand how the brain works at the systems levels. Most recent projects focus on only brain neurons, with the exception of an early effort to reconstruct the 302 neurons that comprise the whole body of the small worm,Caenorhabditis elegans. However, to fully elucidate the neural circuitry of complex behavior, it is crucial to understand brain interactions with the whole body, which can be achieved only by mapping the whole-body connectome. In this article, we discuss the current state of connectomics study, focusing on novel optical approaches and related imaging technologies. We also discuss the challenges encountered by scientists who endeavor to map these whole-body connectomes in large animals.This article is based on a Presidential Lecture presented at the 2016 Annual Meeting.