 Acne vulgaris is an under-studied common genetic disease with tremendous economic consequences. Acne vulgaris is one of the most common skin conditions treated by doctors. It affects 40-50 million people in the USA, with prevalence as high as 85 recent study from Iran was 93 in teenagers; 18 of woman have late onset 25yr acne vulgaris. Severe acne has a life-long psychosocial impact due to the significant scarring. Severe acne can also be associated with severe systemic inflammatory disease with fever, sterile osteomyelitis, inflammatory arthritis and other signs of systemic inflammatory responses. Some of these syndromes in Mendelian form e.g. PAPA syndrome have known genetic defects. Finally, while the data are inconclusive, there have been many suggestions that diet can exacerbate acne in some patients. The standard of care treatment for severe acne is systemic retinoid therapy, which, is usually, but not always effective. Unfortunately, systemic retinoid treatment is associated with significant toxicity, including common cutaneous adverse effects dry lips, eyes, skin fragility, less common laboratory abnormalities such as elevated blood lipids, liver function abnormalities, and severe predictable teratogenicity. In addition, systemic therapy with retinoids has been associated with systemic diseases such as clinical depression, suicide, and inflammatory bowel disease, however the mechanisms and significance of these associations has not been determined. Given the frequency and severity of severe acne, the predictable severe toxicity of systemic retinoid therapy, and the already demonstrated genetic associations found in Mendelian forms of severe acne, it seems likely that significant genetic risk factors may be identified in patients with severe acne which would promote new and safer therapy, including dietary adjustment. 