In this review, we present some different and special conditions that are generally being treated with anticoagulants such as cerebral vein thrombosis (CVT), mesenteric vein thrombosis (MVT), Budd-Chiari syndrome (BCS), and Pulmonary Hypertension (PH) despite the lack of controlled clinical trials. While either low molecular weight heparins (LMWHs) or unfractioned heparin (UFH) are used in the acute phase of the first three conditions, the potential chronic use of warfarin in PH is controversial. What is not completely known in the management of CVT, MTV, and BCS is whether (a) LMWHs are similar to UFH in terms of efficacy and safety, and (b) a fibrinolytic drug could be employed in the acute phase. The timing at which warfarin should be started, and the duration of its employment are two additional crucial points that deserve to be examined. In the course of PH, the role of warfarin is controversial, but it could be employed after a careful balance of the hemorrhagic and thromboembolic risk. In conclusion, we tried to simplify the approach to this sometimes problematic task considering the available literature with the aim of providing some practical skills to be used by physicians in their daily clinical practice. Since it is improbable that in the future controlled clinical trials will be designed to find the optimal anti-thrombotic management of these conditions, we believe that a physician should be aware of the lack of solid data in the field but at the same time should always exert clinical judgment when considering an aggressive anticoagulant approach. The duration of oral anticoagulant treatment is left to the clinical judgment of the balance between the hemorrhagic and thrombotic risks in any single patient.