Global industrialization is meeting the needs of the modern world at the expense of increased exposure to numerous pollutants such as heavy metals (HMs) throughout the ecosystem. Environmental adulteration has been a significant cause of concern. HMs have a direct effect on the quality of water and soil. Once these substances enter the food chain, they are deemed deleterious for human health, even at concentrations marginally higher than those necessary for normal metabolism. Consumption of HM-intoxicated water and food and inhalation of contaminated air obviously causes multiple pathologies. The importance of gut microbial ecosystem or resident gut bacterial diversity has greatly been recognized in various aspects of human health and diseased conditions. Due to the advancement of sequencing technologies, the genomic information of non-culturable microbial species is efficiently being extracted and their potential role in host physiology is predicted in an unprecedented manner. Recently, the impact of HM toxicant exposure on this previously unnoticed organ (gut microflora) has been documentedk which suggested that the direct impact of these HMs on various pathological conditions could deeply be rooted in their ability to alter this gut microbial ecosystem. This chapter discusses some of the key HM toxicants and their impact on the resident gut microbial architecture and the two-way interaction between them by summarizing the findings from recent literature.