The increasing worldwide prevalence of type 2 diabetes (T2D) motivates efforts to use genetics to define key pathways involved in disease predisposition, and thereby to improve management of the disease. Research over the past 5 years has taken the total number of genetic loci implicated in T2D susceptibility beyond 60, and the emphasis is now shifting to the translation of these genetic insights into clinical value. Clinical translation may flow from the identification of novel therapeutic targets, but opportunities also exist with respect to individual prediction, diagnostic biomarkers and therapeutic optimization. To date, the main clinical impact has been seen for relatively rare, monogenic forms of diabetes rather than common T2D. However, the advent of high throughput sequencing approaches may herald discovery of rare and low frequency variants that offer greater translational potential.