During the last decade we have witnessed an unprec-edented outburst of new treatment approaches for the management of metastatic colon cancer.Anti-angio-genic drugs,epidermal growth factor receptor blockers and multi-kinase inhibitors have all resulted in small but consistent improvement in clinical outcomes.However,this progress has paradoxically leaded us into new chal-lenges.In many cases the clinical development was done in parallel and the lack of head-to-head compari-son evolved into circumstances where several valid new“standards of care”are available.Even though desir-able in essence,the availability of many options as well as different possible combinations frequently leaves the busy clinician in the difficult situation of having to choose between one or the other,sometimes without solid evidence to support each decision.In addition,progress never stops and new agents are continuously tested.For these reason this review will try to summa-rize all the clinical trials that constitute the theoretical framework that support our daily practice but will also procure the reader with rational answers to common clinical dilemmas by critically appraising the current literature.Lastly,we will provide with a compilation of promising new agents that may soon become our next line of defense against this deadly disease. During the last decade we have witnessed an unprec-edented outburst of new treatment approaches for the management of metastatic colon cancer. Anti-angio-genic drugs, epidermal growth factor receptor blockers and multi-kinase inhibitors have all resulted in small but consistent improvement in clinical outcomes.However, this progress has paradoxically leaded us into new chal- lenges.In many cases the clinical development was done in parallel and the lack of head-to-head compari-son evolved into where several valid new “standards of care ”are available.Even though desir-able in essence, the availability of many options as well as different possible combinations frequently leaves the busy clinician in the difficult situation of having to choose between one or the other, sometimes without solid evidence to support each decision.In addition, progress never stops and new agents are also tested. These reasons reason this review will try to summarize all the clinical trials that con stitute the theoretical framework that support our daily practice but will also procure the reader with rational answers to common clinical dilemmas by critically appraising the current literature. Lastly, we will provide with a compilation of promising new agents that may soon become our next line of defense against this deadly disease.