The technique of microneurography-recording neural traffic from nerves in awake humans-has provided us with unrivaled insights into afferent and efferent processes in the peripheral nervous system for over 50 years. We review the use of microneurography to study single C-fiber afferents and provide an overview of the knowledge gained, with views to future investigations. C-fibers have slowly conducting, thin-diameter, unmyelinated axons and make up the majority of the fibers in peripheral nerves (~80%). With the use of microneurography in humans, C-fiber afferents have been differentiated into discrete subclasses that encode specific qualities of stimuli on the skin, and their functional roles have been investigated. Afferent somatosensory information provided by C-fibers underpins various positive and negative affective sensations from the periphery, including mechanical, thermal, and chemical pain (C-nociceptors), temperature (C-thermoreceptors), and positive affective aspects of touch (C-tactile afferents). Insights from microneurographic investigations have revealed the complexity of the C-fiber system, methods for delineating fundamental C-fiber populations in a translational manner, how C-fiber firing can be used to identify nerve deficits in pathological states, and how the responses from C-fibers may be modified to change sensory percepts, including decreasing pain. Understanding these processes may lead to future medical interventions to diagnose and treat C-fiber dysfunction. NEW & NOTEWORTHY The technique of microneurography allows us to directly investigate the functional roles of single C-fiber afferents in awake human beings. Here we outline and discuss the current field of C-fiber research on this heterogeneous population of afferents in healthy subjects, in pathological states, and from a translational perspective. We cover C-fibers encoding touch, temperature, and pain and provide perspectives on the future of C-fiber microneurography investigations in humans.