The epithelial lining of the small intestine mediates its absorptive and secretory function and thus is a critical component of human health. Regeneration and renewal of the epithelium is the result of proliferation of intestinal stem cells (ISCs). Many cell types and molecular factors are known to regulate the ability of ISCs to proliferate, including adjacent neighboring epithelial cells and the underlying, supportive stromal cells. The microbiome resides in the lumen of the small intestine and is in close contact with the epithelium. Due to its proximity to ISCs, it has been hypothesized that species within the microbiome have the capacity to regulate ISC proliferation and differentiation. This review highlights research that probes interactions between ISCs and the microbiome in the small intestine to detail the current understanding of microbial regulation of ISCs. Results from these studies provide important knowledge that can be exploited to identify therapeutic targets or develop novel preventative treatments to treat intestinal diseases.