Advances in antiemetic therapy for cancer patients have been hindered by a lack of understanding of the physiological mechanisms associated with nausea and their corresponding measurement techniques. Here we review conceptual and methodological issues involved in developing an autonomic frame of reference for nausea and outline two strategies for assessing autonomic function. A primarily research-oriented strategy uses heart rate, blood volume pulse, pallor, and skin temperature to assess autonomic activity and reactivity over 24 hr. Peak values of these measures relative to time of emesis, heart rate spectral analyses of autonomic activity, and analyses of the standard deviation of successive differences of beat-to-beat intervals were all associated with subsequent nausea. A primarily clinically oriented strategy assesses normal and abnormal results on eight common bedside clinical tests of autonomic function. The total number of abnormal tests was associated with subsequent nausea. A better understanding of chemotherapy side effect mechanisms is likely to result in less polypharmacy and more effective individualized treatment for cancer patients.