Cardiovascular disease (CVD) remains the most common cause of premature death in the chronic kidney disease (CKD) population. Individuals with CKD are at 10-20 times greater risk of cardiac death than controls without CKD, despite stratification for age, race, sex and diabetes. Heightened CVD mortality begins with mild kidney disease and rises further with more advanced kidney disease. Traditional risk factors account for up to 50% of cardiovascular disease in CKD, whilst renal specific markers, including anemia, disordered bone mineral metabolism and oxidative stress, also likely contribute to the total cardiovascular burden in CKD. Despite the increased mortality, there has been a dearth of interventional cardiovascular randomized controlled trials (RCTs) in the CKD population. Furthermore, many patients with kidney disease have been excluded from the majority of mainstream cardiovascular interventional trials. While recently published RCTs on traditional and non-traditional risk factors including dyslipidemia (PPP, 4D and ALERT, VA-HIT), cardiomyopathy (FOSIDIAL, telmisartan, carvedilol), anemia (US Normal Hematocrit, CHOIR and CREATE trials), hyperhomocystenemia (ASFAST, US folic acid trial, HOST), disordered bone mineral metabolism (Cunningham meta-analysis, DCOR), oxidative stress therapy (SPACE, HOPE and ATIC, N-acetylcysteine) and multidisciplinary multiple cardiovascular risk factor intervention clinics (LANDMARK) have added to the available pool of clinical data, level 1 clinical evidence remains significantly lacking. The negative findings in many of these trials highlight the potential dangers of extrapolating findings from non kidney disease patients to those with CKD. Further large, well-designed trials are urgently required to address this issue.