Pyrrolizidine alkaloids (PAs) are widely distributed among higher plants, with over 650 PAs produced by more than 6 000 plants. Only a limited number of PAs of bacterial origins are discovered. For example, clazamycin A and B, reported by Umezawa in 1979 were among the firstly discovered bacterial PAs. In recent years, driven by microbial genomics and synthetic biology, the discovery and study of bacterial PAs and their biosynthetic mechanisms have made impressive progresses. To date, 12 types of PAs (~60) derived from bacteria have been identified, including bohemamines, azetidomonamides, and brabantamides, as well as polyene macrolactam ciromicins and heronamides containing PA structural units. The biosynthetic study of several PAs results in the identification of a unique pair of non-ribosomal peptide synthetase/Bayer-Villiger monooxygenase responsible for the formation of the pyrrolizidine skeleton. In contrast, the formation of the pyrrolizidine unit in β-amino acids polyene macrolactams might involve a highly diastereoselective electrocyclization process. Further, microbial genome mining reveals a lot of silent PAs biosynthetic gene clusters in bacteria, indicating that PAs play an important role in bacterial evolution and adaptation of their environment/hosts.