Many clinical trials have been conducted on the treatment of pityriasis rosea (PR). Our aim was to establish a position statement for the management of adults with PR based on the best available evidence. We searched PubMed for all reports on randomized controlled trials for the treatment of PR published in the past 30 years. We retrieved 14 articles reporting randomized controlled trials, and found five which met our quality requirements for in-depth analyses. Erythromycin was found in a well-conducted triple-blind study to cast significant impacts on clinical outcomes. However, adverse gastrointestinal effects were fairly common. Another well-conducted study on azithromycin reported no significant benefit. It was reported in three well-conducted studies on oral acyclovir in low dose (400 mg three times daily for 7 days or 400 mg five times daily for 7 days) and high dose (800 mg five times daily for 7 days), that acyclovir is effective in attaining rash regression and lessening the pruritus. When compared against each other, the high-dose regimen demonstrated no benefit over the low-dose regimens. Our statement comprises the follows: (i) The diagnosis of PR should be ascertained; (ii) The patients should be assessed for rash severity and impacts on quality of life; (iii) PR is a self-limiting disease, and most patients do not necessitate any treatment; (iv) For patients necessitating active treatment, oral acyclovir as 400 mg three times daily for 7 days can be considered; (v) Attention should be given to adverse effects and contraindications of acyclovir; (vi) When PR occurs in early pregnancy, oral antiviral therapy could be considered after consulting experienced clinicians; (vii) Inadequate information exists in the use of acyclovir to treatment PR in children and breastfeeding women; and (viii) Treating PR is an off-label use of acyclovir, and this has to be discussed with experienced colleagues and the patients.