Symptomatic thromboembolic complications of central venous catheters (CVCs) occur in 5% or less of general oncology patients. Asymptomatic CVC-related thrombi are more common, but their clinical significance is unclear. Thrombotic risk may be increased by primary thrombophilic disorders, especially the factor V G1691A (Leiden) mutation, thrombogenic catheter material, larger catheter diameter and greater number of lumens, catheter tip malposition, left-sided placement, percutaneous or multiple insertion attempts, a previous CVC or preexisting venous obstruction, prothrombotic therapeutic agents, catheter-associated infections, and fibrinous catheter lumen occlusion. Three recent randomized, prospective, placebo-controlled trials observed no benefit of routine low-dose warfarin or low-molecular-weight heparin in preventing catheter-associated thrombosis. Nevertheless, thromboprophylaxis may be appropriate and safe for selected high-risk patients. Duplex ultrasound can accurately detect CVC-related thrombi involving the jugular, axillary, distal subclavian, and arm veins. Contrast venographic imaging is required for indeterminate duplex findings and to evaluate the deep central veins and pulmonary arteries. Therapeutic anticoagulation, with or without catheter removal, is indicated for patients with acute deep vein thrombosis (DVT) or pulmonary embolism who have no contraindications. Catheter removal alone, with close follow-up, may be sufficient when bleeding risk precludes safe anticoagulation. Approaches to managing catheter-associated thrombosis, including the use of thrombolytic agents, are guided by limited published experience and extrapolation from practices used for lower-extremity DVT. Prospective, randomized, controlled trials are needed to identify the safest and most effective anticoagulant agents, treatment durations, and alternative venous access strategies for cancer patients who develop catheter-associated thrombosis.