Glucocorticoids (GC) remain the most commonly used agents for managing inflammatory rheumatic diseases. The adverse effects (AEs) associated with high-dose GCs are well established, but there is a widespread misconception that AEs of high-dose GC therapy (>30 mg of prednisone or equivalent daily) are similar in low-dose therapy (≤7.5 mg of prednisone equivalent a day). Although high-quality evidence on AEs of low-dose GC therapy is still incomplete, risks and safety of low-dose GC therapy in rheumatic diseases are reviewed based on current evidence by category, including musculoskeletal, cardiovascular, infectious, gastrointestinal, neuropsychiatric, endocrine and metabolic, dermatologic, and ophthalmologic AEs. Recommendations concerning monitoring AEs with low-dose GC therapy are provided for each category of AEs on the basis of our literature review and clinical experience. There is emerging evidence that low-dose GCs are associated with a much lower level of AEs, which would allow their use over long periods in patients with rheumatic disease who gain clinical effectiveness and well-being from their use. Nonetheless, knowledge and understanding of AEs from low-dose GCs is vital to maximize benefits and minimize risks to patients.