The natural product antibiotic fidaxomicin is a marketed drug for the treatment of bacterial infections in the gut. Due to its promising in vitro activities against Mycobacterium tuberculosis, the development of next generation fidaxomicin analogs is of great interest. This article reviews the most recent advances, including the elucidation of a unique mode of action by cryo-EM structures, and the efforts towards the clarification of the biosynthetic pathway. Moreover, known fidaxomicin analogs and their reported antibacterial activities are summarized.