Colorectal cancer (CRC) is the fourth most common cancer in the world. If detected at an early stage, treatment often might lead to cure. Of course prevention is better than cure. Epidemiological studies reveal that having a healthy diet often protects from CRC development. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are a number of agents making their way into clinical trials by estimating their effects on biomarkers expression. Also, some are awaiting the preclinical efficacy and safety results to enter into clinical trials. Oncologic researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the biological and analytical perspective. However, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target agents needs to be evaluated in appropriate animal models for their efficacies as well as toxicities. This review focuses on the few of the potential molecular targets and their biomarkers in CRC development.