Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. There is substantial evidence in advanced cancer that host factors, such as weight loss, poor performance status and the host systemic inflammatory response, are linked, and the latter is an important tumor-stage-independent predictor of outcome. Indeed, the systemic inflammatory response, as evidenced by an elevated level of C-reactive protein, is now included in the definition of cancer cachexia. This review examines the role of the systemic inflammatory response in predicting survival in patients with primary operable cancer. Approximately 80 studies have evaluated the role of the systemic inflammatory response using biochemical or hematological markers, such as elevated C-reactive protein levels, hypoalbuminemia or increased white cell, neutrophil and platelet counts. Combinations of such factors have been used to derive simple inflammation-based prognostic scores, such as the Glasgow Prognostic Score, the neutrophil:lymphocyte ratio and the platelet:lymphocyte ratio. This review demonstrates that there is now good evidence that preoperative measures of the systemic inflammatory response predict cancer survival, independent of tumor stage, in primary operable cancer. The evidence is particularly robust in colorectal (including liver metastases), gastro-esophageal and renal cancers. As described in this article, measurement of the systemic inflammatory response is simple, reliable and can be clinically incorporated into current staging algorithms. This will provide the clinician with a better prediction of outcome, and therefore better treatment allocation in patients with primary operable cancer. Furthermore, systemic inflammation-based markers and prognostic scores not only identify patients at risk, but also provide well-defined therapeutic targets for future clinical trials.