For patients who fail traditional acne therapy or experience side effects, other treatments are needed. Cephalexin has been noted to be efficacious in some instances. This study aimed to assess the therapeutic efficacy of cephalexin for acne. A retrospective chart review of 93 acne patients treated with cephalexin was performed. Data collection included patient demographics, other acne therapies, clinical response, and side effects. Of the 98 courses of cephalexin, 4% of patients cleared, 45% were much improved, 29% were somewhat improved, 16% experienced no change, and 6% worsened at first follow-up visit. The median treatment length was 6 months. Eighty-four percent of patients had previously used a systemic antibiotic(s) for acne. Seven percent experienced adverse effects. This is a small retrospective analysis without a comparison group and is limited by the number of patients and nonstandardized treatment lengths and charting procedures. Cephalexin is a promising alternative treatment for acne, with 78% of patients exhibiting at least some clinical improvement.