Acyclic nucleosides are primarily considered for the treatment of anogenital herpes simplex despite these drugs are available during several decades for management of herpes infection. However, modern sights about the negative impact of herpes simplex virus make it possible to take a broader view on the issue of episodic and prolonged therapy of herpes infection considering immune disorders associated with recurrent disease. Systemic pathological processes are associated with recurrent infection and cover almost all directions of clinical medicine rather dermato-venereological practice alone. Unfortunately, little attention is still paid to these aspects. There are various states when herpes simplex virus per se has direct or indirect etiological role. However, these states are often not recognized by clinicians as an indication for administration of acyclic synthetic nucleosides. Episodic and prolonged administration of acyclic nucleosides for recurrent herpes simplex infection is analyzed considering perennial own experience, national and foreign data. Data are based on immunological features observed in recurrent herpes simplex infection of various severity. Two types of pathogenetic processes were identified for recurrent herpes infection which were caused by both the virus per se and specific antibodies. These data confirm that antiviral therapy with acyclic synthetic nucleosides is the most effective and safe in various clinical situations regardless mode of therapy.