Physicians are not always aware that locally administered glucocorticoids can cause systemic toxicity. This risk is greatly enhanced in the case of pharmacological interactions. We present two cases of HIV-infected patients who developed Cushing-like symptoms as a result of a pharmacological interaction. Their antiretroviral treatment regimen consisted of atazanavir, ritonavir, tenofovir and emtricitabine. One patient received salmeterol/fluticasone inhalations for asthmatic bronchitis. The other was treated with intra-articular triamcinolonacetonide injections for ongoing shoulder complaints. Ritonavir exhibits strong inhibition of hepatic enzyme CYP 3A4, which is part of the major metabolic pathway of most glucocorticoids. As a result of this interaction even locally administered glucocorticoids can cause symptoms of overdose, e.g. Cushing-like symptoms. Beclomethasone is a safe alternative for inhaled glucocorticoids as it is not metabolized by CYP 3A4. There is no substitute for intra-articular administration of triamcinolonacetonide. Depending on necessity of the administration of the drug, changing ritonavir-containing antiretroviral therapy to a non-interacting compound, e.g., an integrase inhibitor, is an option.