Enteroviruses are the most common human viral pathogens worldwide. This genus of small, non-enveloped, single stranded RNA viruses includes coxsackievirus, rhinovirus, echovirus, and poliovirus species. Infection with these viruses can induce mild symptoms that resemble the common cold, but can also be associated with more severe syndromes such as poliomyelitis, neurological diseases including aseptic meningitis and encephalitis, myocarditis, and the onset of type I diabetes. In humans, polarized epithelial cells lining the respiratory and/or digestive tracts represent the initial sites of infection by enteroviruses. Control of infection in the host is initiated through the engagement of a variety of pattern recognition receptors (PRRs). PRRs act as the sentinels of the innate immune system and serve to alert the host to the presence of a viral invader. This review assembles the available data annotating the role of PRRs in the response to enteroviral infection as well as the myriad ways by which enteroviruses both interrupt and manipulate PRR signaling to enhance their own replication, thereby inducing human disease.