Functional connectomics enables researchers to monitor interactions among thousands of units within the whole brain simultaneously by using various vivo imaging technologies. For example, resting-state functional magnetic resonance imaging can image low-frequency fluctuations in the spontaneous brain activities, representing a popular tool for macro-scale functional connectomics to characterize individual differences in normal brain function, mind-brain associations, and the various disorders. Reliability and reproducibility represents the most fundamental and critical aspect for the human brain functional connectomics to both research and clinical practice. Unfortunately, lacking a data platform for researchers to rigorously explore the reliability and reproducibility of the functional connectome indices has been a bottleneck of further development of clinically oriented imaging markers in the field. Recent efforts on open neuroscience, such as Consortium for Reliability and Reproducibility, Human Connectome Project and OpenFMRI, provide the data for the field to refine and evaluate reliability and reproducibility of novel methods as well as those with widespread usage but without sufficient consideration of reliability. This Frontiers Research Topic aims at bringing together contributions from researchers in brain imaging, neuroscience, computer sciences, applied mathematics, psychology and related fields from an interdisciplinary perspective. By focusing on cutting-edge research across these fields, this topic will create new agenda on quantifying the reliability and reproducibility of the myriad connectomics-based measures and informing expectations regarding the potential of biomarker discovery.