Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic diseases such as IBDs (inflammatory bowel disease, ulcerative colitis, Crohn’s disease) amebiosis, colon cancer), degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. To achieve successful colon targeted drug delivery, a drug need to be protected from degradation, release and absorption in the upper portion of the GI tract and then to be ensured controlled release in the proximal colon. Many prodrugs have been evaluated for colon drug delivery. These prodrugs are designed to pass intact and unabsorbed from the upper GIT and undergone biotransformation in the colon releasing the active drug molecule by variety of enzymes, mainly of bacterial origin present in the colon (e.g. azoreductase, glucuronidase, glycosidase, dextranase, esterase, nitroreductase, cyclodextranase etc.). Treatment of these diseases with colon-targeted drug delivery system provides an interesting alternative over systemic drug administration because of lower dosing and fewer systemic side effects. This review will cover various natural prodrug conjugates and recent pharmaceutical approaches to colon targeted drug delivery system.