Every human cell contains the same set of genes, yet only a small proportion of these are active at any one time in particular cell types. Array technology is allowing measures of upregulation or downregulation or aberrant forms of expression of many genes simultaneously, and these changes can be related to diseases and traits. For several cancers, gene-expression signatures have led to new understanding of the disease and are being used clinically to target treatment. Recent studies of circulating white cell gene expression changes in the Invecchiare in Chianti (InCHIANTI) cohort suggest that deregulation with age is relatively limited, with a small minority of expressed genes showing strongly age-related changes in expression. Changes in the format of expressed transcripts (so-called splicing changes) were also identified: these suggest that white cells are losing fine tuning of gene expression. Expression changes with muscle strength and cognition have highlighted the role of macrophage-mediated clean up and regeneration processes and have confirmed mouse models. Challenges for the future include access to other tissues, and studying gene expression changes over time.