Inflammatory markers such as the ESR and CRP are valuable tools for the diagnosis and management of rheumatic diseases along with other blood parameters such as the white blood cells and platelets. However, their interpretation must take into account several parameters, or else diagnostic errors and inappropriate treatments may ensue. This may be the case in several instances as inflammatory markers are not specific to rheumatic diseases only and may result from other causes such as infections, malignancies or metabolic disorders. Conversely, normal titres of inflammatory markers do not always exclude an active rheumatic disease, especially when it comes to the early stage of a disease or conditions like fibromyalgia and seronegative spondyloarthropathies. Systemic lupus erythematosus also is a rheumatic disease that may be active without elevated inflammatory markers (except in cases of active arthritis and serositis). Clinicians should always correlate inflammatory markers with the present clinical findings, consider alternative diagnoses and use additional diagnostic tools such as musculoskeletal ultrasound and other imaging techniques and disease-specific markers. Misinterpretation of ESR, influenced by factors like age, gender and current anaemia, neglecting in parallel the dynamic nature of CRP, can further complicate diagnosis and monitoring of the patients. For diseases where inflammatory markers are less informative, the clinician should pay attention to clinical evaluation. By recognising the limitations of inflammatory markers and correlating them with the clinical picture of the patients, diagnostic accuracy will definitely be better improving patient outcomes.