Metagenomic analyses have revealed microbial dysbiosis in the gut of patients with colorectal cancer (CRC). The gut microbiota influences CRC via a variety of mechanisms, including microbial-derived factors such as metabolites or genotoxins. Pathogenic drivers and opportunistic passenger bacteria may underlie direct effect of the gut microbiota on carcinogenesis. We posit that metabolites generated by gut microbiota can influence CRC through a multitude of epigenetic or genetic effects on malignant transformation. A closer look at the cross talks between the commensals, epithelial cells, immune regulators etc., needs to be established with more substantiated studies. The recurrence of chemoresistant disease following therapy undoubtedly provides the impetus for morbidity and mortality; yet, the role of gut microbiome in drug resistance remains to be fully investigated. We review the current literature on microbial dysbiosis during CRC and discuss the mechanistic basis of CRC-associated bacteria in tumor initiation, progression and drug resistance.