Erythema Multiforme is an acute, self-limited inflammatory cutaneous disorder characterized by distinctive target lesions. Stevens-Johnson syndrome (SJS) is defined as severe erythema multiforme with mucosal involvement, visceral involvement, or both. Both diseases are part of a continuum of immunologically mediated mucocutaneous diseases at various grades of severity. Viral infections are known triggers of these skin disorders. We report the success of a management strategy of acyclovir and prednisone for herpes simplex virus-associated erythema multiforme. In addition we describe the apparent first case of primary varicella infection as a direct cause of SJS. The two cases are presented and a single-case statistical analysis has been employed to evaluate the significance of the management protocol. The method of analysis is presented in the appendix. When a patient with primary varicella infection develops bullous lesions, SJS should be considered in the differential diagnosis, as early and intense corticosteroid therapy may be lifesaving. A regimen of prophylactic acyclovir and therapy for an exacerbation of herpetic lesions with acyclovir and prednisone was effective in inducing significant control of recurrent erythema multiforme secondary to herpes simplex in our patient.