Bottom-up synthetic biology aims to construct mimics of cellular structure and behaviour known as artificial cells from a small number of molecular components. The development of this nascent field has coupled new insights in molecular biology with large translational potential for application in fields such as drug delivery and biosensing. Multiple approaches have been applied to create cell mimics, with many efforts focusing on phospholipid-based systems. This mini-review focuses on different approaches to incorporating molecular motifs as tools for lipid membrane functionalization in artificial cell construction. Such motifs range from synthetic chemical functional groups to components from extant biology that can be arranged in a ‘plug-and-play’ approach which is hard to replicate in living systems. Rationally designed artificial cells possess the promise of complex biomimetic behaviour from minimal, highly engineered chemical networks.