Primary Cicatricial Alopecias (PCAs) are a group of skin diseases in which there is progressive and permanent destruction of hair follicles followed by replacement with fibrous tissue. Unfortunately, by the time patients seek clinical evaluation of their hair loss, the skin is already inflamed and/or scarred, so there is little hope for a return to their normal hair growth pattern. Clinical and basic science investigations are now focusing on three forms of human PCA, lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and central centrifugal cicatricial alopecia (CCCA). Transcriptome, lipidome, and other new technologies are providing new insight into the pathogenesis of some of these diseases that are being validated and further investigated using spontaneous and genetically engineered mouse models. This article is protected by copyright. All rights reserved.