The pathogenesis of acute myocardial infarction (AMI) involves a sudden thrombotic occlusion of a coronary artery. Spontaneous or pharmacologic thrombolysis may lead to myocardial salvage if patency is achieved within a narrow time window. However, patients in whom thrombolysis occurs late seem to demonstrate improved left ventricular (LV) function and prognosis, which may be independent of myocardial salvage. Preservation of normal LV geometry by reducing expansion of the infarcted segment is a likely mechanism for this benefit. Infarct expansion is most pronounced in patients with anterior wall AMI who have a persistently occluded infarct-related vessel. This process of expansion leads to early increases in LV volume and distortions of LV contour (abnormal LV geometry). Patients whose infarct segment is largest, patients who have manifested infarct expansion, and patients with a persistently occluded infarct-related artery are at highest risk for progressive LV dilation. Experimental data support the concept that reperfusion of occluded vessels that occurs too late for myocardial salvage will preserve LV geometry by limiting infarct expansion. Prospective clinical trials should address whether there is a late, "second time window" during which infarct expansion and distortions of LV geometry may be reduced by (1) therapy with thrombolytic agents applied late after infarction, (2) late mechanical reperfusion with percutaneous transluminal coronary angioplasty (PTCA) or related methods, and (3) load-reducing agents to decrease remodeling, such as angiotensin-converting enzyme inhibitors or nitroglycerin.