AbstractThe study of the origin of life and current undergoing efforts to produce artificial chemical systems mimicking the behavior of natural living systems have emerged as a hot topic at the interfaces among disciplines. In these two problems, the spontaneous generation of free‐energy gradients by means of material interfaces plays a central role and, until recently, hindered progress. Polymerization‐induced self‐assembly (PISA) is a promising strategy for the formation of polymeric vesicles from a homogeneous mixture which, in the form of artificial biology, may reflect and inform the generation of vesicular structures in primitive Earth. In the past few years, PISA has been used for the construction of biomimetic vesicles or artificial protocells in artificial biology. These not only give inspiration for decoding some aspects of the origin of life in arbitrary environments but also offer potential for building innovative functional systems with a wide variety of applications. In this review, a brief summary of some of the unique possibilities offered by PISA and the development of PISA in exploration of artificial biology is provided, while some of the allied current challenges, limitations, and opportunities in this exciting field are highlighted.