Introduction Viral skin diseases are common in humans, with the majority causing infection in children and immunocompromised individuals. According to Acton (2013), viral skin disease and infections occur in almost every community and region in the world. While some infections are common among people living in certain geographic regions, others are distributed worldwide. Among the most common viral infections in humans are plantar warts and hands, foot and mouth disease. Different viruses cause the two infections, but clinical manifestations in both types of infection are characterized with the appearance of wars and marks on the skin. The purpose of this paper is to examine each of the infections, the nature of the viruses involved and make a comparison based on these areas. Plantar Warts infection Overview A plantar wart is a skin disease caused by infection with human papilloma virus (HPV). According to James et al (2006), the common clinical name of the disease is Verruca plantis, which indicates that the disease occurs on toes of the foot. The aim is to distinguish between plantar warts (infection with HPV on toes) from other HPV infections on other parts of the body, where warts are also a major form of manifestation. According to Shulman and Pod (2005), plantar warts are self-limiting, which means that the infection reaches a point at which it heals without clinical attention. However, the lesions involved are painful and can cause the transmission to other persons. As such, treatment is recommended to decrease the rate of transmission and severity of pain. Epidemiological studies in the US indicate that about 10% of the population suffers from the disease once or more in life. However, some countries like China and India, though with high populations, have lower incidence rates. For instance, according to, James et al (2006), China and India record less than 1% incident rates of the disease every year. According to a study by Mallory, Baugh and Parker (2001), the most probable cause of these differences can be determined genetically. For instance, genetic studies have shown that whites are more susceptible to warts than Asians and blacks. Causes of the disease: The HPV virus Human Papilloma Virus (HPV) belongs to the viral family papillomaviridae that includes a number of DNA viruses that affect animals such as humans, birds, turtles and snakes. The family have a naked or non-enveloped DNA as its genome and each species has a number of sub-species. Differences are noted according to the types of animal infected, the part of the body infects as well as genomic sequences. Majority of the HPV are known to cause no harm in humans. However, warts (verrucae) are the most common manifestation in humans. In addition, recent studies have revealed that HPV infection in the genitals is linked with cervical cancer. In addition, other studies have further shown the existence of a strong link between HPV infection and the development and severity of the cardiovascular disease. Moreover, Gillison (2004) has also shown that oropharynx infection with HPV is linked with the development of oroppharyngeal (throat) cancer. The virology of HPV has extensively been studied ove