Beginning with the pioneering work of Heymans and collaborators in the 1930’s, investigations into the role of the mammalian carotid body (CB) in the control of ventilation have attracted much attention. Progress for many years was restricted to the whole animal and organ level, resulting in characterization of the stimulus-response characteristics of the CB with its afferent nerve supply during exposure to chemostimuli such as low PO₂ (hypoxia), elevated PCO₂ (hypercapnia), and low pH (acidity). Major advances on the cellular and molecular mechanisms of chemotransduction occurred ˜20 years ago with the use of freshly-dissociated CB preparations and single cell studies using patch clamp and spectrofluorimetric techniques. This review will focus on more recent advances based on novel preparations including co-cultures of isolated CB receptor clusters and dispersed sensory or autonomic neurons, thin CB tissue slice preparations, and transgenic models. These preparations have contributed significantly, not only to our understanding of the transduction and neurotransmitter mechanisms that operate in the CB during sensory processing, but also to the identification and characterization of novel CB stimuli such as hypoglycemia. Though the complexity of this remarkable organ still belies its tiny size, these recent advances are slowly unraveling the intricacies surrounding its ability to act as a polymodal detector of blood-borne chemicals and to alter its sensitivity to patterned stimuli.