Previous data indicate that persistent pain states often involve sensitization within the central nervous system (CNS). Many recently described human genetic variants may affect these central processes. Genetic variability influences both synthesis and function of proteins affecting the plasticity of the CNS. Hence, individual genetic variability may be important to understand the development of many persistent pain conditions including chronic nonmalignant back pain. In this review we argue that genotyping of each patient may be a valuable complement to diagnosis of back disorders. This may be important for future prescription of medicine to individuals predisposed for persistent pain. Increased understanding of genetic variability may also improve multidisciplinary and cognitive-behavioral approaches to management of persistent pain. Translation of this information from the laboratory into clinical application will be important for future prevention as well as treatment of long-lasting non-malignant pain conditions.