Synthetic cells constructed via bottom-up strategies represent versatile platforms for investigating the fundamental principles and biological processes of life and developing novel biotechnological applications. This chapter provides an overview of the conceptual foundations, historical evolution, and technological advancements in the field, with particular emphasis on compartmentalized systems based on giant unilamellar vesicles (GUVs). These cell-sized compartments serve as key chassis for encapsulating and integrating biochemical functional modules such as genetic circuits, metabolic pathways, and energy-producing systems. The historical progression from early coacervate models to modern liposome-based protocells is traced, highlighting pivotal milestones in membrane self-assembly, in-vesicle gene expression, and photosynthetic energy production. State-of-the-art techniques for GUV fabrication—including gentle hydration, electroformation, droplet-transfer, and advanced microfluidics—are reviewed with a focus on membrane asymmetry, cargo encapsulation efficiency, and scalability. Furthermore, the emerging capacity of synthetic cells to exhibit stimulus-responsiveness, intercellular communication, and collective behaviours is examined, particularly in the context of prototissue formation positioning them as promising tools for tissue engineering, diagnostics, and soft robotics. Ultimately, the convergence of synthetic biology, soft matter, biophysics and microengineering, is driving the field toward the realization of programmable, biomimicking systems. These developments pave the way for transformative applications in drug delivery, diagnostics, regenerative medicine, and the study of life’s origins.