Primary and recurrent venous thromboembolic disease (VTE, deep venous thrombosis and pulmonary embolism) remain a significant source of morbidity and mortality in the hospitalized patient. Non-specific subjective complaints and lack of specific objective findings related to acute deep venous thrombosis (DVT) and pulmonary embolism (PE) complicate the diagnosis. There remains no single serum marker available to exclusively confirm the diagnosis of VTE. While D-dimer is highly sensitive and useful for diagnostic exclusion, it lacks the specificity necessary for diagnostic confirmation resulting in the need for a variety of additional studies (i.e.: duplex ultrasound, venography, V/Q scanning, helical thoracic and pelvic CT scans and pulmoary angiography). There is evolving research supporting the utility of various plasma markers as novel "biomarkers" for VTE including selectins, microparticles, interleukin-10 and other cytokines. This review attempts to examine recent literature assessing the utility of P-selectin, microparticles, D-dimer, E-selectin, thrombin, interleukins and fibrin monomers in the diagnosis and guidance of therapy for VTE.