A rapidly acting anticoagulant that can either inhibit thrombin generation or inhibit thrombin itself is the optimum therapy for acute thrombosis associated with heparin-induced thrombocytopenia (HIT). In this review, the newer treatment approaches that fulfill this requirement are discussed. These newer treatments include hirudin and argatroban, direct thrombin inhibitors, and danaparoid, which inhibits thrombin generation. Preliminary outcome results from the extensive compassionate-use program for danaparoid in HIT and from a recently completed randomized clinical trial that compared danaparoid with dextran in patients with HIT are provided. Based on these data, danaparoid appears to be a useful and safe replacement for heparin in patients who develop HIT.