The pharmacological management of nonspecific chronic low back pain (NCLBP) aims to restore patients’ daily activities and improve their quality of life. The management of NCLBP is not well codified and extremely heterogeneous, and residual symptoms are common. Pharmacological management should be considered as co-adjuvant to non-pharmacological therapy, and should be guided by the symptoms reported by the patients. Depending on the individual severity of NCLPB, pharmacological management may range from nonopioid to opioid analgesics. It is important to identify patients with generalized sensory hypersensitivity, who may benefit from dedicated therapy. This article provides an evidence-based overview of the principles of pharmacological management of NCLPB.