Peripheral blood mononuclear cells (PBMCs) generally refer to monocytes and lymphocytes, representing cells of the innate and adaptive immune systems. PBMCs are a promising target tissue in the field of nutrigenomics because they seem to reflect the effects of dietary modifications at the level of gene expression. In this review, we describe and discuss the scientific literature concerning the use of gene expression at the mRNA level measured from PBMCs in dietary interventions studies conducted in humans. A search of literature was undertaken using PubMed (last assessed November 24, 2011) and 20 articles were selected for discussion. Currently, results from these studies showed that PBMCs seem to reflect liver environment and complement adipose tissue findings in transcriptomics. PBMC gene expression after dietary intervention studies can be used for studying the response of certain genes related to fatty acid and cholesterol metabolism, and to explore the response of dietary interventions in relation to inflammation. However, PBMC transcriptomics from dietary intervention studies have not resulted yet in clear confirmation of candidate genes related to disease risk. Use of microarray technology in larger well-designed dietary intervention studies is still needed for exploring PBMC potential in the field of nutrigenomics.