Mycobacterial carbonic anhydrases, such as the essential protein Rv3588c, are attractive drug targets since they constitute a different class of carbonic anhydrases than those found in humans. A natural product library has been screened for compounds that inhibit mycobacterial carbonic anhydrases but lack the much-exploited sulfonamide/sulfamate group. The identified inhibitors of mycobacterial Rv3588c are likely to affect the enzyme at a site different from the catalytic centre – a concept which may be exploited for novel specific anti-mycobacterials.