Spurred by advances in understanding the molecular basis of thrombosis, this issue of the Journal of Thrombosis and Thrombolysis is devoted to exploring aspects of novel paradigms and their potential impact on diagnosis and treatment. Complex interplay between blood and vascular cells, inflammation, and pro- and anti-coagulant pathways determines the formation and stability of arterial and venous thrombosis. A causal role for inflammation in coronary artery disease is currently being tested in large clinical trials. Basic science observations implicate inflammation in venous thromboembolic disorders and inflammatory processes, may have a similar influence on device thrombosis. In this article and throughout this issue of the Journal, we discuss biomarkers and mediators associated with arterial and venous thrombosis, atrial fibrillation, and other clinical scenarios.