Future solar-to-chemical production will rely upon a deep understanding of the material-microorganism interface. Hybrid technologies, which combine inorganic semiconductor light harvesters with biological catalysis to transform light, air and water into chemicals, already demonstrate a wide product scope and energy efficiencies surpassing natural photosynthesis. But optimization to economic competitiveness and fundamental curiosity beg for answers to two basic questions: 1) how do materials transfer energy and charge to microorganisms, and 2) how do we design for bio- and chemo- compatibility between these seemingly unnatural partners? This Perspective highlights the state-of-the-art and outlines future research paths to inform the cadre of spectroscopists, electrochemists, bioinorganic chemists, material scientists and biologists that will ultimately solve these mysteries.