Methotrexate was widely introduced as a new DMARD (disease-modifying antirheumatic drug) for the treatment of rheumatoid arthritis in the mid-1980s. It is still highly relevant despite or precisely because of the numerous drugs that have since been approved for various inflammatory diseases, not just in the field of rheumatology, but also in dermatology and gastroenterology. This comprehensive work on methotrexate as monotherapy and as a combination partner answers all questions for clinical practice based on the current state of knowledge and is intended to serve as a daily companion for the practitioner.