The ocular surface is the first line of defence in the eye against environmental microbes. The ocular innate immune system consists of a combination of anatomical, mechanical and immunological defence mechanisms. TLRs (Toll-like receptors), widely expressed by the ocular surface, are able to recognize microbial pathogens and to trigger the earliest immune response leading to inflammation. Increasing evidence highlights the crucial role of TLRs in regulating innate immune responses during ocular surface infective and non-infective inflammatory conditions. In addition, recent observations have shown that TLRs modulate the adaptive immune response, also playing an important role in ocular autoimmune and allergic diseases. One of the main goals of ocular surface treatment is to control the inflammatory reaction in order to preserve corneal integrity and transparency. Recent experimental evidence has shown that specific modulation of TLR pathways induces an improvement in several ocular inflammatory conditions, such as allergic conjunctivitis, suggesting new therapeutic anti-inflammatory strategies. The purpose of the present review is to summarize the current knowledge of TLRs at the ocular surface and to propose them as potential targets of therapy for ocular inflammatory conditions.