In Part 1 of this review, we discussed how plaque rupture is the most common underlying cause of most cases of unstable angina/non-ST-segment-elevation myocardial infarction (UA/NSTEMI) and how early risk stratification is vital for the timely diagnosis and treatment of acute coronary syndromes (ACS). Now, in Part 2, we focus on the medical therapies and treatment strategies (early conservative vs early invasive) used for UA/NSTEMI. We also discuss results from various large randomized controlled trials that have led to the contemporary standards of practice for, and reduced morbidity and death from, UA/NSTEMI. In summary, ACS involving UA/NSTEMI is associated with high rates of adverse cardiovascular events, despite recent therapeutic advances. Plaque composition and inflammation are more important in the pathogenesis of ACS than is the actual degree of arterial stenosis. As results from new trials challenge our current practices and help us develop the optimal treatment strategy for UA/NSTEMI patients, the cornerstones of contemporary treatment remain early risk stratification and aggressive medical therapy, supplemented by coronary angiography in appropriately selected patients. An early-invasive-treatment strategy is of most benefit to high-risk patients, whereas an early-conservative strategy is recommended for low-risk patients. Adjunctive medical therapy with acetylsalicylic acid, clopidogrel or another adenosine diphosphate antagonist, glycoprotein IIb/IIIa inhibitors, and either low-molecular-weight heparin or unfractionated heparin, in the appropriate setting, further reduces the risk of ischemic events secondary to thrombosis. Short- and long-term inhibition of platelet aggregation should be achieved by appropriately evaluating the risk of bleeding complications in these patients.