Colorectal cancer (CRC) is a common cancer affecting approximately 4% of people. CRC arises through multiple genetic events and can affect intestinal homeostasis. Healthy intestinal epithelium acts as a physical barrier separating the intestinal microbiota from the host. The barrier is formed by tightly linked intestinal epithelial cells (IECs), which constantly self-renew, shed, and actively communicate with the microbiota. Signaling pathways affecting intestinal cell fate and homeostasis may therefore alter functions related to intestinal barrier homeostasis and even cause cancer. One critical signaling pathway involved in CRC development is KRAS. KRAS family proteins are involved in IEC proliferation, self-renewal, differentiation, adhesion, and apoptosis, and KRAS mutations occur in 45% of CRC patients, with most mutations locking the protein in an active conformation. Thus, KRAS is in a unique position: while it is critical for intestinal homeostasis, its overactivation results in uncontrolled proliferation of stem cells, possibly resulting in cancer. While less clear, KRAS family members may also play roles in signaling at epithelial junctions, signaling between intestinal cells and the microbiota, and immune-mediated inflammation. Scientists are focused on improving our understanding of signaling networks downstream of KRAS and how they affect cancer development and progression, with the potential to transform personalized medicine for CRC.