This review about the proactive sequential therapy (PST) of external genital and perianal warts (EGW) is based on the most current available clinical literature and on the broad clinical experience of a group of international experts, physicians who are well versed in the treatment of human papillomavirus-associated diseases. It provides a practical guide for the treatment of EGW, including epidemiology, etiology, clinical appearance, and diagnostic procedures for these viral infections. Furthermore, the treatment goals and current treatment options, elucidating provider- and patient-applied therapies, and the parameters driving treatment decisions are summarized. Specifically, the mode of action of the topical treatments sinecatechins and imiquimod, as well as the PST for EGW to achieve rapid and sustained clearance is discussed. The group of experts has developed a treatment algorithm giving healthcare providers a practical tool for the treatment of EGW which is very valuable in the presence of many different treatment options.