Lemierre Syndrome is a rare form of septic thrombophlebitis of the head and neck veins, most typically of the internal jugular vein, which affects otherwise healthy adolescents and young adults after an oropharyngitis or other local infection. It is characterized by multiple septic embolization. Despite treatment, Lemierre Syndrome displays a high rate of in-hospital complications that include thrombus progression and a new peripheral septic embolization; moreover, it can be fatal or cause disabling sequelae. The mainstay of the treatment is antibiotic therapy; anticoagulation is often used, but its role is controversial. Surgical treatment is often necessary in case of peripheral septic lesions. In the absence of prospective studies, what little guidance exists on its management is based on case series or on analogy with similar conditions, such as other forms of septic thrombophlebitis or non-septic venous thrombosis. Over the last few years, new observational evidence has improved our knowledge of the clinical epidemiology of this condition and highlighted a number of promising management strategies. We provide an overview of the treatment patterns adopted in the contemporary era, and summarize the arguments proposed so far against or in favor of alternative treatments as well as possible decision rules on the use of anticoagulation. Moreover, we outline the priorities of ongoing and future observational and interventional research.