Sudden Cardiac Death (SCD) is responsible for an estimated 300,000 US deaths per year. Despite sophisticated resuscitation techniques and first responder systems, survival rates are very low. This is especially true for the majority of cases where the onset is unexpected and without prior cardiac symptoms; and further underscores the importance of finding better ways of early identification of subjects at risk of SCD. Although important contributions have been added from cohort studies as well as community-based studies, more pieces of the puzzle need to be solved. The use of plasma biomarkers is a common instrument for assessing cardiovascular risk in different subsets. In this review, we weigh the evidence regarding a potential role for plasma biomarkers in predicting SCD in the general population and suggest future investigative approaches that could be of clinical utility.