Ketoconazole is an antifungal commonly used for symptom management of inflammatory skin diseases, such as dandruff and seborrheic dermatitis (D/SD). 1 Traditionally, lipophilic yeasts from Malassezia genus have been associated with D/SD; however, their role as causal agents has been questioned. 2 It has been shown that ketoconazole susceptibility varies among species, S1 and mechanisms of resistance have been described in dandruff-isolated strains. S2 Clinical trials indicate that ketoconazole is efficient in managing D/SD symptoms S3 ; however, they did not assess antifungal activity directly.Using quantitative RT-PCR, we have previously shown that amounts of Malassezia and total fungi did not decrease in SD patients under ketoconazole therapy. 3 Nevertheless, symptoms improved, suggesting mechanisms of action other than antifungal activity. There is evidence of immunosuppressive activity, S4 but it is not sufficient for explaining symptom improvement. The lipid composition of stratum corneum is potentially important for skin barrier disruption and chronic inflammation; and Malassezia metabolites, such as fatty acids and indoles, have been implicated in stratum corneum damage. S5 We argue that ketoconazole shifts host lipid profile from skin, which affects Malassezia lipid metabolism. The resulting alteration in lipid availability, including Malassezia-produced fatty acids, impacts bacterial communities and favours biotin-producing bacteria. Biotin has been implicated in inflammatory response, cell proliferation and biosynthesis of fatty acids 4 potentially improving symptoms of D/SD (Figure 1).In order to investigate effects of ketoconazole in D/SD skin homeostasis, we performed bioinformatics analyses. Chemical-protein interaction database surveys (Appendix S1) indicated that ketoconazole interacts with cytochrome enzymes (Figure S1). Functional analysis revealed lipid and steroid metabolism pathways (Table S1), suggesting that ketoconazole shifts sebum secretion. Ketoconazole-associated host and Malassezia lipid profile shifts might affect bacterial microbiota. It has been shown that