The Critical Path Initiative was announced in 2004 and was the result of a reexamination of priorities of the FDA including pre-market and post-market issues impacting all the product review centers. The discovery, validation and ultimately the inclusion of biomarkers in medical decision-making is a high priority for FDA. Several biomarkers were identified as being important in the Critical Path Opportunities List issued in March 2006 by the FDA. Markers for adverse events in drugs and/or vaccines, markers for disease progression, surrogate outcomes for drug eluting stents are among the list of markers FDA believed would impact medical practice. I will focus on prognostic and predictive biomarkers in particular. I will also discuss as an example the deNovo clearance (in February 2007) of the Mammaprint prognostic marker for early stage breast cancer.