Background The clinical syndrome of unstable angina has multiple causes; different therapies therefore may be indicated in different patients. Methods Recent publications on unstable coronary artery disease were reviewed to identify pathophysiologic phenomena and concepts that can aid decision-making in the clinical management of patients with unstable coronary artery disease of different causes. Results The fate of any coronary plaque depends on local and systemic factors. Autopsy studies have revealed that plaques most likely to rupture are those with a soft lipid core covered by a thin fibrous cap that may be inflamed. Systemic Factors such as hypertension may be maximally expressed at the site of plaques that are prone to rupture. If an unstable plaque is identified, local therapy, such as angioplasty, stents, or radiation, and aggressive systemic therapy, such as lipid lowering, diabetes control, and hypertension control, can be used. Conclusions Specific therapy for acute symptoms can be used if the specific cause of the unstable state can be identified. Failure of the plaque to stabilize may result in recurrent ischemia, biochemical evidence for myocardial damage, and evidence of an inflammatory process. These factors influence prognosis; cardiac events occur more commonly when they are present.