Isolated distal deep vein thrombosis (DVT), also known as calf DVT, represents up to 50% of all lower limb DVT in ultrasound series and is therefore a frequent medical condition. Unlike proximal DVT and pulmonary embolism (PE), which have been extensively studied and for which management is well standardized, much less is known on the optimal management of isolated calf DVT. Recent data arising from registries and non-randomized studies suggest that most distal DVTs do not extend to the proximal veins and have an uneventful follow-up when left untreated. This data had some impact on the international recommendations which recently stated that ultrasound surveillance instead of systematic therapeutic anticoagulation might be an option for selected low-risk patients. However, robust data arising from randomized studies are scarce. Indeed, only five randomized trials assessing the need for anticoagulation for calf DVT have been published. Many of these trials had an open-label design and were affected by methodological limitations. The only randomized placebo-controlled trial included low-risk patients (outpatients without cancer or previous venous thromboembolic events (VTE)) and was hampered by a limited statistical power. Nevertheless, data from this trial tend to confirm that the use of therapeutic anticoagulation in low-risk patients with symptomatic calf DVT is not superior to placebo in reducing VTE, but is associated with a significantly higher risk of bleeding. Further randomized studies are needed to define the best therapy for high-risk patients (inpatients, patients with active cancer or previous VTE), and the optimal dose and duration of treatment.