whi genes, named after the mutations turning Streptomyces coelicolor colonies into white, exist largely in Actinomyces and Mycobacterium. whiB genes, a subclass of whi, involve in wide range of events, such as cell division, spore formation, nutrient starvation, pathogenesis, antibiotic resistance, and stress sense. To better understand the role of this family in physiology and pathology in the important pathogen-Mycobacterium tuberculosis, WhiB and WhiB-like proteins function and structures of were bioinformatically dissected. Seven WhiB proteins can be found in M. tuberculosis genome, most are highly conserved. Based on the data mining of published microarray profiling of wild type and mutants transcriptome response to diverse treatments, a regulatory network of whiB is established. Some findings from this network are obvious. WhiB2 and WhiB7 might be key nodes in drug resistance, WhiB3 might involve in the maintenance of redox homeostasis. These works provide new Mycobacterium persistence and virulence hypothesis for future experimental validation.