Fatigue is a prominent symptom in many rheumatic diseases. Numerous factors contribute to cause fatigue, which can be a source of frustration for the patients and physicians, as the treatment often fails to produce the desired improvement. Diagnostic guidelines direct insufficient attention to the various semiological patterns of fatigue seen in rheumatic diseases. This update describes three main patterns of fatigue, depending on whether the source is physical or mental: muscle weakness in patients with neuromuscular disease; asthenia related to organic disease with excessive energy expenditure, deficient energy production (e.g., endocrine disorders), or inadequate recovery; and weariness due to the impact of stress and depression on quality of life. The prevalence of each pattern in various rheumatic diseases is discussed. This update underlines the practical benefits provided by a detailed semiological analysis of fatigue in patients with rheumatic disease and emphasizes the marked predominance of weariness due to stress and depression, on which the personality of the patient and inadequacy of social support systems may exert a major influence. Serotonin reuptake inhibitors (SSRIs) may be valuable in patients with fatigue not only because they improve the mental status, but also via their recently demonstrated anti-inflammatory effects.