The picornaviruses are a diverse group of viral pathogens that together comprise the most common causes of infection of humans in the developed world. Within the picornavirus family are three well-known groups of human pathogens - the rhinoviruses, the enteroviruses (including polioviruses, coxsackieviruses and echoviruses) and the hepatoviruses (including hepatitis A virus). This article will focus on the rhinoviruses and enteroviruses, agents for which substantial effort has been expended, and recent successes reported, toward the development of safe and effective antiviral therapy.