Toll-like receptors (TLRs) are key players in maintaining protection against any invading pathogen. These molecules are microbial sensing proteins which detect pathogen-associated molecular patterns and induce the body's innate immune system to elicit a response against invading pathogens. In addition to their role in pathogen recognition and elimination, these proteins are highly important in cancer biology and also play a variety of roles in normal to cancerous transformation or its prevention. There is much published literature on the role of TLRs in pathogen recognition and elimination, but recently the number of articles relevant to the role of TLR in carcinogenesis has increased due to their importance in this area. On the one hand, they are involved in microbial elimination and, on the other hand, their modulation during cancer development has several implications. Accumulating a diverse thread of cancer-associated TLR modulation and infection susceptibility has several caveats. Some cancer-associated TLR modulation increases susceptibility to particular infections, while increased expression of certain TLR was found to help in the carcinogenic process through inducing inflammation. This article concludes that clinicians should consider TLR modulation during infection risk assessment in cancer patients. These modulations should also be considered while designing management strategies against cancer and its associated infections.