Recently, some Indian states reported an outbreak of a ‘mysterious illness’ involving more than a hundred children younger than nine years, with fever and skin lesions. These lesions were more prominent and manifested in the palms, soles, oral cavity, and other body parts. This was initially considered to be a new illness and was described as ‘tomato flu’. The disease was contagious but found to be mild in severity. Later in time, it has been identified to be a hand, foot and mouth disease (HFMD), caused by Coxsackievirus-16 (CA-16). So, the term ‘tomato flu’ should not be used since it is a misnomer for this disease. The mild and uncomplicated HFMD cases usually did not require any antiviral therapy. CA-16 may be associated with a severe, life-threatening HFMD, especially in children with immunocompromised, malnourished, chemotherapy, or underlying medical conditions. However, there are some antiviral agents, intravenous immunoglobulin (IVIG), and vaccines available for the treatment and prevention of HFMD. In this review, we have observed that acyclovir and oseltamivir were effective for patients with serious forms of HFMD. In some cases, the administration of antiviral agents along with IVIG was proven to be more effective. Out of the antiviral agents studied, we observed that oseltamivir and acyclovir were effective with less adverse effects. Three inactivated whole-virus EV-71 vaccines have been licensed, while a recombinant VP1 vaccine against CA-16 is under development. Many types of research revealed that there are many potential and prospective antiviral candidates that can be employed in the near future. The antiviral drug umifenovir (arbidol) was found to be very effective against HFMD under in vivo laboratory conditions. There were some prospective antiviral agents, required to pass through phases of clinical trials.