The integration of genetic, behavioral, and engineering techniques has enabled us to chart the heterogeneous cellular and circuit organization of the brain with unprecedented resolution. Yet, the emerging brain atlas is both illuminating and perplexing in its complexity. How do brain circuit elements interoperate and give rise to the panoply of behavioral and cognitive functions? Recent developments in cell-specific perturbation technologies are beginning to give researchers the ability to reverse engineer intact neural circuits, by directly probing the activities, connections, and underlying molecular properties of specific neurons. Our latest developments have focused on three directions: 1) expanding the repertoire of genetically-encoded neuromodulators for controlling a variety of cellular functions from electrical signal to transcriptional activities, 2) developing better genome engineering systems using Transcription Activator-like Effectors (TALEs) and microbial CRISPRs, and 3) integrating these tools with a variety of readout methods. The emerging technology platform combining optogenetics and precise genome engineering tools enables deconstruction of previously inaccessible brain circuits, and will improve our understanding of the causal relationship between circuit activities and brain function.