Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States. However, more than half of all incidence and mortality are caused by risk factors such as smoking, unhealthy diet, excessive alcohol consumption, inactivity, and excess weight, and thus can be protected. CRC morbidity and mortality can also be reduced by proper screening and monitoring. Over the last few years the amalgamation of nanotechnology with healthcare system has brought about the potential to administer the delivery of certain therapeutic drugs to cancer cells without affecting normal tissues. Recent strategies combine the diagnostic and therapeutic approaches to improve the overall performance of cancer nanomedicines. Targeted cancer nanotherapeutics provides many more opportunities for the selective detection of toxic chemicals within cancer cells. The distinctive features of nanoparticles, such as their small size, large surface to volume ratio, and the ability of nanoparticles to achieve several interactions of ligands at surface, offer great benefits of nanomedicines to treat various types of cancers. This review highlights the molecular mechanisms of colorectal carcinogenesis and discusses various key concepts in the development of nanotherapeutics targeted for CRC treatment.