Transcriptional profi les have been obtained from many human tissues -including, for instance, the skin [5, 6] , muscle [7] , liver [8, 9] , kidney [10, 11] or brain [12] -but the status of the immune system can be best monitored by profi ling transcript abundance in blood. Indeed, profi ling transcript abundance in blood provides a 'snap shot' of the complex immune networks that operate throughout the entire body. However, while this has proven to be a valid approach to fi nding clues about The number of high-throughput molecular and cellular profi ling tools that can be used to profi le the human immune system is increasing rapidly. Proteomic assays are used to determine antibody specifi city or measure changes in serum levels of cytokines or chemokines using multiplex assays. Cellular profi ling assays are used to phenotype immune cells based on intracellular or extracellular markers using polychromatic fl ow cytometry. In vitro cellular assays can measure innate or antigen-specifi c responsiveness in cells exposed to immunogenic factors. Genomic approaches consist of measuring abundance of cellular RNA and also microRNAs that are present in cells or in the serum. Other genomic approaches consist of determining gene sequence and function (for example, genome-wide association studies, RNA interference screens, exome sequencing). patho genesis as well as to identifying potential biomarkers [13] [14] [15] [16] , a number of challenges and limitations exist. Data interpretation is one of them. Firstly, the volume of data generated from such studies can be overwhelming, and it is necessary to integrate information from a multitude of sources (study design, quality control data, sample information, and importantly clinical information) in order for the results to be interpretable. Secondly, the changes in transcript abundance observed in complex tissues such as blood can be caused not only by regulation of gene transcriptional activity but also by relative changes in abundance of cell populations expressing transcripts at constant levels. Th irdly, in addition to pathogenic processes, a number of factors may aff ect blood transcript abundance and confound the analysis. Medications and co-morbidities are two such factors that often restrict patient selection and complicate data interpretation. Th is review will discuss some of the strategies recently developed that will address some of these limitations.