Dalbavancin and oritavancin are newer long-acting antibiotics with potent activity against gram-positive organisms, including MRSA. Their prolonged half-life, 257 hours for dalbavancin and 195 hours for oritavancin, allows for less frequent dosing. However, a long half-life also leads to prolonged drug exposure, should adverse effects occur. Here we report the first case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient treated with dalbavancin and oritavancin.