Lipopeptides are a group of second metabolites ofBacillusand have multiple activities such as inhibiting fungi, bacteria, viruses, and tumors, showing a great potential application in agricultural and biomedical fields. However, low production severely restrained their application in practice. Deeply understanding the key elements of lipopeptide synthesis and the regulatory strategies is essential to target the improvement of lipopeptide production. The synthetic pathways of different lipopeptides are different, but closely and mutually interfered. The loading of fatty acid chains and the extension of peptide chains are two key steps for the synthesis of different lipopeptides byBacillus. The selection of fatty acid chains, the loading order of amino acids, and the recognition of the final cyclization site are the critical steps to determine the end products of different lipopeptides. In order to find the key elements for precisely directing the formation of different lipopeptides byBacillus, the key structural elements and possible regulatory strategies that have been reported in the production of different lipopeptides, mainly surfactin, iturin, and fengycin byBacillus, were summarized and compared. The possible ways to improve the production of different targeted lipopeptides were proposed.