The liquid-solid interface is a unique medium to support the self-assembly of molecules into surface-confined networks. Non-covalent interactions are key in forming these two-dimensional (2D) architectures, and a deep understanding is crucial for successful 2D crystal engineering. Scanning tunnelling microscopy is the tool of choice to reveal the structure and function of these patterns with subnanometre resolution. A recent success is the formation of 2D nanoporous molecular patterns and their host guest chemistry. However, this is not the only functionality addressed by this review. Surface-confined molecular architectures at the liquid solid interface are also relevant in the field of molecular electronics. Furthermore, inducing and probing chemical reactivity at the single-molecule level at the liquid solid interface might turn out to be one of the most exciting developments.