Clinicians should be aware of the differences in corticosteroid formulations as these differences dictate which agent is best in various clinical situations. Corticosteroids work primarily by modulating transcriptional, post-transcriptional, and post-translational mechanisms within cellular nuclei to decrease the production of inflammatory mediators. Because this process requires change at the cellular level, clinical effects typically take days. The main consideration when selecting a corticosteroid is solubility. Less-soluble agents have a longer onset of action and a longer duration. However, they can have negative side effects on soft-tissue structures. They are ideal for intra-articular use. More-soluble agents have a faster onset of action but are rapidly cleared. They are ideal for extra-articular soft-tissue structures. Fluorinated compounds have decreased solubility, which further increases duration of action, but they have been shown to be associated with tendon rupture and atrophy.