Significant progress and new insights have been gained since the Dutch Physical Therapy guideline on low back pain (LBP) in 2013 and the Cesar en Mensendieck guideline in 2009, necessitating an update of these guidelines. To update and develop an evidence-based guideline for the comprehensive management of LBP and lumbosacral radicular syndrome (LRS) without serious specific conditions (red flags) for Dutch physical therapists and Cesar and Mensendieck Therapists. Clinically relevant questions were identified based on perceived barriers in current practice of physical therapy. All clinical questions were answered using published guidelines, systematic reviews, narrative reviews or systematic reviews performed by the project group. Recommendations were formulated based on evidence and additional considerations, as described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. Patients participated in every phase. The guideline describes a comprehensive assessment based on the International Classification of Functioning, Disability and Health (ICF) Core Set for LBP and LRS, including the identification of alarm symptoms and red flags. Patients are assigned to three treatment profiles (low, moderate and high risk of persistent symptoms) based on prognostic factors for persistent LBP. The guideline recommends offering simple and less intensive support to people who are likely to recover quickly (low-risk profile) and more complex and intensive support to people with a moderate or high risk of persistent complaints. Criteria for initiating and discontinuing physical therapy, and referral to a general practitioner are specified. Recommendations are formulated for information and advice, measurement instruments, active and passive interventions and behavior-oriented treatment. An evidence based physical therapy guideline for the management of patients with LBP and LRS without red flags for physical therapists and Cesar and Mensendieck therapists was developed. Cornerstones of physical therapy assessment and treatment are risk stratification, shared decision-making, information and advice, and exercises.