The year 2016 marks 50 years since the publication of the seminal paper by Hatch and Slack describing the biochemical pathway we now know as C4 photosynthesis. This review provides insight into the initial discovery of this pathway, the clues which led Hatch and Slack and others to these definitive experiments, some of the intrigue which surrounds the international activities which led up to the discovery, and personal insights into the future of this research field. While the biochemical understanding of the basic pathways came quickly, the role of the bundle sheath intermediate CO2 pool was not understood for a number of years, and the nature of C4 as a biochemical CO2 pump then linked the unique Kranz anatomy of C4 plants to their biochemical specialization. Decades of “grind and find biochemistry” and leaf physiology fleshed out the regulation of the pathway and the differences in physiological response to the environment between C3 and C4 plants. The more recent advent of plant transformation then high-throughput RNA and DNA sequencing and synthetic biology has allowed us both to carry out biochemical experiments and test hypotheses in planta and to better understand the evolution-driven molecular and genetic changes which occurred in the genomes of plants in the transition from C3 to C4. Now we are using this knowledge in attempts to engineer C4 rice and improve the C4 engine itself for enhanced food security and to provide novel biofuel feedstocks. The next 50 years of photosynthesis will no doubt be challenging, stimulating, and a drawcard for the best young minds in plant biology.