Small molecules that bind to proteins can serve as powerful medicines. However, diseases caused by deficiencies of protein function can be refractory to this classic approach. Fortunately, nature has provided inspiration for an alternative strategy in the form of small molecules that can perform higher-order, protein-like functions in the context of living systems. These include the ion channel forming polyene macrolide amphotericin B, the antilipoperoxidant carotenoid peridinin, and the energy transducing chromophore retinal. The existence of these natural prototypes suggests that small molecules may possess untapped potential to replace deficient proteins that underlie human diseases, thereby operating as prostheses on the molecular scale. Relative to their protein counterparts, however, the functions of these natural products remain poorly understood which currently precludes effective harnessing of this higher-order functional potential. Importantly, recent advances in synthetic organic chemistry stand to play a major role in better understanding these molecules. Specifically, analogous to iterative peptide coupling, iterative cross-coupling with MIDA boronates has emerged as a powerful and increasingly general way to prepare complex small molecules with maximized efficiency and flexibility, thereby enabling systematic studies of their functions. Collectively, these developments stand to help promote the advanced understanding and ultimately widespread utilization of small molecule surrogates for human proteins.