Although there have been recent advances in the treatment of metastatic colorectal cancer, particularly with systemic chemotherapy, new biological agents and surgical metastasectomy, the disease remains difficult to treat. To personalise the management of mCRC and optimise patient outcomes, it is vital to acquire a deeper understanding of its natural history and mechanisms behind disease progression. This may be achieved by extensive study of tumour biomarkers: proteins or genetic alterations within neoplastic cells or their surrounding stroma that may be used to predict patient outcomes, disease trajectory and response to various therapies. The discovery of mutant Kirsten-RAS in determining patients who may be refractory to anti-epidermal growth factor receptor treatments has reinvigorated and reiterated the importance of our attempts to individualise cancer care. While many biomarkers have been studied and shown promise in the setting of mCRC, they are, with the exception of K-ras testing not used currently in a clinical setting due to conflicting results, small patient samples and methodological variations. Larger, multi-centric studies with uniform methods of tumour marker study are required to effectively tailor systemic therapies and select appropriate candidates for surgical metastasectomy.