Survival of all animals depends on an accurate representation of the world, and an organism must be capable of prioritizing and responding to potentially hazardous conditions. This ability is dependent on nociception, the sensory process allowing animals to detect and avoid potentially harmful stimuli. Nociception is the sensory process that results in the subjective experience of ‘pain’ in humans. Because of its vital and broad role in animal biology, pain/nociception is a complex, whole-body physiological process that is under stringent evolutionary pressure. Here, we discuss the utility of Drosophila melanogaster as an emerging model organism for studying the conserved genetics of nociception, particularly with respect to recently developed high-throughput Drosophila ‘pain’ paradigms.