The emergence of multiple-drug-resistant strains of bacteria, the indiscriminate use of antibiotics and the increasing susceptibility of individuals with acquired immunodeficiency syndrome (AIDS) to infection from Mycobacterium induce an urgent need for development of new strategies to treat bacterial infections. Many natural products from marine sources are endowed with promising antibacterial activities, thus representing invaluable leads in the plans for antibiotic drug discovery. In this context, organic synthesis plays a decisive role in confirming (or revising) the chemical structures of the natural compounds allowing also access to suitable amounts of the target (and its analogs) for structureactivity relationship (SAR) investigations. In this overview, we focus on the total and partial synthesis of antibacterial marine metabolites and their related compounds published since 2000, discussing the retrosynthetic analysis of the strategies adopted. It includes the total synthesis of pestalone, squalamine, abyssomicin C and litosterol, the revised structure by total synthesis for the antituberculosis pseudopteroxazole and agelasine C, the preparation of the core-structure of zamamistatin and access to momeric and dimeric congeners of active peptide halocidin. Review with 132 references.