Antimicrobial resistance is a rapidly growing problem worldwide, with bacteria showing resistance to last‐resort antibiotic treatments such as carbapenems and colistin becoming more abundant. Synthetic biology may be able to contribute to solving this growing antimicrobial resistance crisis by facilitating the engineering of diversified collections of novel antibiotics, targeting multidrug resistant bacteria in new ways. This review discusses recent advances in the use of synthetic biology methodologies to discover and produce novel antimicrobials; in particular, the work being carried out on biosynthetic gene clusters, heterologous chassis, and synthetic microbial consortia, the “three Cs” of the title.