Glucocorticoids are one of the most frequently prescribed therapies in rheumatology, a reflection of their effectiveness as a powerful anti-inflammatory drug. Glucocorticoids are also, however, associated with a wide range of adverse events, particularly at higher doses. To make appropriate decisions, doctors and patients need to weigh these benefits against the potential harms. This article describes the many uncertainties which make informed prescribing difficult. We lack knowledge, for example, on the magnitude of risk, the relationship to dose and duration, and what happens to risk on stopping therapy. Beyond safety, we describe how patients may lack understanding of the nature of the benefits and harms, and how to incorporate value judgements which are crucial to the decision making process. We conclude by exploring how future research might fill these knowledge gaps to enable a better informed decision process.