Glucocorticoids remain a valuable and necessary component of therapy for many diseases. Nonetheless, sustained glucocorticoid treatment increases potential for future cardiovascular disease through multiple pathways, resulting in a tradeoff between benefit and harm. This article explores the potential mechanisms of glucocorticoid-induced hyperglycemia and dyslipidemia. Interactions between glucocorticoids and other potential cardiovascular risk factors are also reviewed. Safe, alternate strategies for minimizing the need for glucocorticoids are urgently needed.