Collectively, studies published thus far demonstrate that alterations in transcript abundance can be detected on a genome-wide scale in the blood of patients with a wide range of diseases. Th is statement is far from trivial given the skepticism that initially met studies investigating the blood transcriptome of patients. We have also learned that: 1) multiple diseases can share components of the blood transcriptional profi le -for instance, the case for infl ammation or interferon signatures; 2) while no single element of the profi le may be specifi c to any given disease it is the combination of those elements that makes a signature unique; and fi nally, 3) the work accomplished to date highlights the importance of carrying out analyses aiming at directly comparing transcriptional profi les across diseases. Indeed, much can be learned, for instance, about autoimmunity from studying responses to infection, and vice versa. Furthermore, such eff orts may eventually lead us closer to a molecular classifi cation of diseases. First, however, technological and methodological advances are necessary for the blood transcriptome research fi eld to move beyond the proof of principle stage.