Although chronic low back pain (cLBP) is increasingly recognized as a complex syndrome with multifactorial etiology, the pathogenic mechanisms leading to the development of chronic pain in this condition remain poorly understood. This article presents a new, testable pathophysiological model integrating connective tissue plasticity mechanisms with several well-developed areas of research on cLBP (pain psychology, postural control, neuroplasticity). We hypothesize that pain-related fear leads to a cycle of decreased movement, connective tissue remodeling, inflammation, nervous system sensitization and further decreased mobility. In addition to providing a new, testable framework for future mechanistic studies of cLBP, the integration of connective tissue and nervous system plasticity into the model will potentially illuminate the mechanisms of a variety of treatments that may reverse these abnormalities by applying mechanical forces to soft tissues (e.g. physical therapy, massage, chiropractic manipulation, acupuncture), by changing specific movement patterns (e.g. movement therapies, yoga) or more generally by increasing activity levels (e.g. recreational exercise). Non-invasive measures of connective tissue remodeling may eventually become important tools to evaluate and follow patients with cLBP in research and clinical practice. An integrative mechanistic model incorporating behavioral and structural aspects of cLBP will strengthen the rationale for a multidisciplinary treatment approach including direct mechanical tissue stimulation, movement reeducation, psychosocial intervention and pharmacological treatment to address this common and debilitating condition.