Chronic low back pain (CLBP) is pain that has persisted for greater than three months. It is common and burdensome and represents a significant proportion of primary health presentations. For the majority of people with CLBP, a specific nociceptive contributor cannot be reliably identified, and the pain is categorised as 'non-specific'. Exercise therapy is recommended by international clinical guidelines as a first-line treatment for non-specific CLBP. This comprehensive review aims to synthesise and appraise the current research to provide practical, evidence-based guidance concerning exercise prescription for non-specific CLBP. We discuss detailed initial assessment and being informed by patient preferences, values, expectations, competencies and goals. We searched the Cochrane Database of Systematic Reviews, PubMed and the Physiotherapy Evidence Database (PEDro) using broad search terms from January 2000 to March 2021, to identify the most recent clinical practice guidelines, systematic reviews and randomised controlled trials on exercise for CLBP. Systematic reviews show exercise is effective for small, short-term reductions in pain and disability, when compared with placebo, usual care, or waiting list control, and serious adverse events are rare. A range of individualised or group-based exercise modalities have been demonstrated as effective in reducing pain and disability. Despite this consensus, controversies and significant challenges remain. To promote recovery, sustainable outcomes and self-management, exercise can be coupled with education strategies, as well as interventions that enhance adherence, motivation and patient self-efficacy. Clinicians might benefit from intentionally considering their own knowledge and competencies, potential harms of exercise and costs to the patient. This comprehensive review provides evidence-based practical guidance to health professionals who prescribe exercise for people with non-specific CLBP. © 2021 John Wiley & Sons Ltd.