Statin therapy reduces the risk of cardiovascular events in patients with coronary artery disease. Recent in vitro and in vivo studies demonstrated a LDL-independent action of these class of drugs, which appears in modulating endothelial function, inflammation and thrombosis. Periprocedural myocardial infarction and contrast-induced nephropathy after percutaneous coronary intervention (PCI), associated with worse outcome on long-term follow-up, are both complications related to inflammatory pathogenetic mechanisms. Randomized studies demonstrated a beneficial effect of short-term statin pretreatment in reducing periprocedural cardiac marker release in patients undergoing PCI. Statin therapy before elective PCI reduces periprocedural myocardial infarction in patients with stable angina. Furthermore, an acute loading with a high dose of atorvastatin prevents myocardial damage in patients with acute coronary syndromes undergoing early PCI (<48 h). In patients already on chronic statin therapy, a reload with high-dose statins was associated with a significant improvement on 30-day major adverse cardiac event rates. Furthermore, statin therapy at the time of PCI significantly decreased the incidence of contrast-induced nephropathy. This evidence suggests an 'upstream administration' of short-term, high-dose statins in all patients undergoing PCI.