Systemic antibiotics are a key component of the hidradenitis suppurativa (HS) treatment toolkit. While they remain a critical therapeutic modality for HS, there has been a shift away from long-term antibiotic use due to rising concerns regarding antibiotic resistance. Thus, antibiotics are now primarily used to manage acute flares or as a bridge to more sustainable, long-term treatments. Single antibiotic use, such as with a tetracycline, cephalosporin, or amoxicillin-clavulanate, have been shown to reduce lesion counts, alleviate pain, and improve quality of life. Combination regimens, such as trimethoprim-sulfamethoxazole and cephalexin, may be utilized for more severe HS cases or for patients who have failed single agent antibiotics. Intravenous ertapenem may also be utilized as a rescue therapy for particularly recalcitrant and severe cases. Antibiotics are valuable tools in HS management, but mindful and strategic use is essential to minimizing bacterial resistance and associated morbidity.