Corticosteroids are frequently used to treat rheumatic diseases. Their use comes with several well-established risks, including osteoporosis, avascular necrosis, glaucoma, and diabetes. The risk of infection is of utmost concern and is well documented, although randomized controlled trials of short-term and lower-dose steroids have generally shown little or no increased risk. Observational studies from the real world, however, have consistently shown dose-dependent increases in risk for serious infections as well as certain opportunistic infections. In patients who begin chronic steroid therapy, vaccination and screening strategies should be used in an attempt to mitigate this risk.