Unfractionated heparin (UFH) remains the principal antithrombotic agent during percutaneous coronary intervention (PCI) but is associated with significant limitations including an unpredictable anticoagulation dose response, the requirement for frequent monitoring, and transient rebound hypercoagulability. Low molecular weight heparin (LMWH) represents an attractive alternative due to its predictable dose response relationship, superior antithrombotic efficacy and potential for improved clinical safety, and has been used increasingly in patients with acute coronary syndromes prior to coronary angiography. The rationale and existing data regarding the use of LMWH in PCI is summarized and reviewed. Preliminary clinical guidelines for the use of LMWH in the transition from medical stabilization of patients with acute coronary syndromes to invasive management in the catheterization laboratory are presented.