Obesity and low back pain (LBP) are responsible for significant morbidities and financial expenditure. Numerous studies have demonstrated a positive relationship between obesity and LBP, but a concurrent investigation of causality is often omitted. Spinal clinicians routinely prescribe exercise and weight loss for obese patients with LBP, despite a paucity of literature evaluating why obesity might cause LBP or how exercise and weight loss might be suitable treatments for LBP. Etiologies have tended to focus on the biomechanical effects of obesity that lead to excessive loading and degeneration of the lumbar spine. However, recent evidence suggests that systemic inflammation associated with obesity may also be an important contributor to LBP. In this article, the latest evidence investigating the relationship between obesity and LBP is reviewed, an overview of the impact of exercise and weight loss on LBP is provided, and proposed mechanisms connecting obesity, systemic inflammation, and LBP are outlined.