Host genetic factors are emerging as key determinants of disease risk for many cancers. Identifying candidate genes is a major challenge that has to stem from a profound understanding of the pathophysiology of the disease. The Toll-like receptors are important members of the host's innate immune response and their genes have been found to be polymorphic. This genetic variation allows for a more intricate repertoire that enables the host to withstand microbial challenges. While this may be advantageous on a population level, there may be less favourable outcomes for individuals that harbour certain genotypes associated with excessive immune activation and inflammatory drive. The damage is often collateral and is manifest in organs where this chronic inflammation alters normal physiology. A classic example of this paradigm is the Helicobacter pylori-induced gastric cancer model. Another emerging model is prostate cancer where Toll-like receptor polymorphisms have also been found to play a role. In this review, we discuss polymorphisms in Toll-like receptors and give an insight into how they may influence risk of cancer.