The fast growth accompanied with high substrate consumption rates and a versatile metabolism paved the way to exploit Vibrio natriegens as unconventional host for biotechnological applications. Meanwhile, a wealth of knowledge on the physiology, the metabolism, and the regulation in this halophilic marine bacterium has been gathered. Sophisticated genetic engineering tools and metabolic models are available and have been applied to engineer production strains and first chassis variants of V. natriegens. In this review, we update the current knowledge on the physiology and the progress in the development of synthetic biology tools and provide an overview of recent advances in metabolic engineering of this promising host. We further discuss future challenges to enhance the application range of V. natriegens.