Recently, several lines of evidence that indicate a strong link between the development of colorectal cancer (CRC) and aspects of the gut microbiota have become apparent. However, it remains unclear how changes in the gut microbiota might influence carcinogenesis or how regional organization of the gut might influence the microbiota. In this review, we discuss several leading theories that connect gut microbial dysbiosis with CRC and set this against a backdrop of what is known about proximal-distal gut physiology and the pathways of CRC development and progression. Finally, we discuss the potential for gut microbial modulation therapies, for example, probiotics, antibiotics, and others, to target and improve gut microbial dysbiosis as a strategy for the prevention or treatment of CRC.