Staggering advances have been made in our understanding of the genetic basis of human systemic lupus erythematosus (SLE), but has this been sufficient to fulfill early predictions that we could use genetics to provide personalized healthcare? Our current understanding of the genetic etiology of SLE indicates a strong underlying genetic predisposition, mediated by multiple gene variants. Compared with other complex genetic diseases, the disease risk imparted by many of these variants is strong. We argue that, for SLE, this particular combination of genetic effects means that the personalized prediction of disease onset or manifestation is certainly a realistic possibility, although further large-scale genetic studies will be required before this becomes a reality. We speculate that, in the future, genetic information could help guide targeted therapeutic intervention.