Safe, inexpensive, and convenient psoriasis therapy is desirable. Two recent case reports suggested that low-dose naltrexone is effective. Cases from our practice are presented in order to further the evidence of efficacy and safety of low-dose naltrexone in the treatment of psoriasis. Patients included 13 females, 2 males; mean age 57 years; mean psoriasis duration 16 years. Of the patients, 8 had psoriatic arthritis. In the past, 5 had completely failed and 10 had partially responded to =1 topical therapies. Patients used a self-assessed Likert scale on the effect of low-dose naltrexone on their psoriasis: 1 - worse; 2 - unchanged; 3 - slightly improved; 4 - somewhat improved; 5 - marked improvement. The response to 4.5 mg of oral naltrexone was as follows: 8/15 marked improvement; 2/15 somewhat improved; and 5/15 unchanged. Three adverse events included insomnia, diarrhea, and self-limited headache. Marked improvement was seen by 53% of the 15 patients. Low-dose naltrexone regulates lymphocyte responses, reduces cytokine production, and likely reduces mast cell activity. Low-dose naltrexone is safe, inexpensive, and appears be effective in this open-label study.