Along with the hyper production of sebum, some of the other functions like oxidant/antioxidant ratio of the lipids on the skin's surface, synthesis of local androgen, antimicrobial peptides production and synthesis of sapienic acid which is lipid with antimicrobial play a crucial role in acne pathogenesis. Until the middle of the 20th century, inflammation was considered to be the result of seborrhea, follicular keratosis, and microbes acting individually as the cause. However, by the mid-twentieth century, none of the aforementioned factors could fully explain the processes. but a ‘chain of some other factors’ such as bacterial inversion, keratinization follicular opening, sebum alteration and inflammation were responsible for the formation of the lesions. One of the reason for acne is an abnormal reaction to normal levels instead of excess hormone levels. However, association of acne in syndromes with hyperandrogenism, like PCOS, HAIR-AN and SAHA syndromes further highlight the role of androgens. Presence of insulin resistance with high circulating serum insulin as is seen in PCOS and HAIR-AN syndrome highlight the role of insulin growth factor 1 (IGF1) on the keratinisation. Propionibacterium acnes as a causative bacterium responsible for inflammatory lesions has been further augmented by its demonstration in bone biopsies in SAPHO syndrome. Role of inflammation is highlighted, as is also seen in PAPA syndrome. Two of the recent case controlled studies have highlighted the role of high glycemic diet with the same premise of high circulating serum insulin. PAPA syndrome with autosomal dominant inheritance with mutation of gene on chromosome 15 responsible for CD2 binding protein 1 (CD2BP1) and FGFR2 mutations in Apert syndrome and neavus comedonicus lend further support for the hypothesis that genetics may play a role in androgen receptor transactivation and IGF-1 signalling, both of which are important in acne pathogenesis.