Recent efforts to broadly apply genetics to clinical practice have been driven by the rapid advancement of genomic technologies and the discovery of genes associated with disease risk, progression, and treatment response. Yet there remain valid concerns about the complexities and limitations that confront the popular notion of clinical utility of genetics in personalized medicine. Research is still very much in the mode of discovery. The excitement of discovery and applications to diagnostics are well described in each of the articles in this issue. Yet, each article appropriately acknowledges the limitations that need to be overcome to apply new knowledge to clinical practice.