Abstract The oncology patient is often at increased risk of bleeding when thrombolytics are administered. Fortunately, the factors placing the patient at risk are easily identified and include intracranial disease, vascular defects produced by surgery, instrumentation or tumor invasion, underlying coagulopathy, and severe thrombocytopenia. Unfortunately, new clot-specific agents have not eliminated the problem of undesirable bleeding; in fact, they may cause more bleeding by more efficiently dissolving both pathological thrombi and hemostatic plugs. The development of a means of delivering thrombolytics solely to the target clot is desirable and should be performed when possible. Despite the need for caution, thrombolytics are remarkably effective in treating both venous and arterial thrombi, and it is a disservice to the patient not to carefully consider their use.