Research addressing the burden, assessment, and management of nonpain symptoms associated with advanced illness in older adults is limited. While nonpain symptoms such as fatigue, sleep, dyspnea, anxiety, depression, cognitive impairment, nausea, and anorexia-cachexia are commonly noted by patients and clinicians, research quantifying their effects on quality of life, function, and other outcomes are lacking and there is scant evidence regarding management. Most available studies have focused on relatively narrow conditions (e.g., chemotherapyinduced nausea) and there are almost no data relevant to patients with multiple morbidities or multiple concurrent symptoms. Assessment and treatment of nonpain symptoms in older adults with serious illness and multiple comorbidities is compromised by the lack of data relevant to their care. Recommended research priorities address the documented high prevalence of distressing symptoms in older adults with serious illness, the unique needs of this population due to coexistence of multiple chronic conditions along with physiologic changes related to aging, the lack of evidence for effective pharmacologic and nonpharmacologic interventions, and the need for validated measures that are relevant across multiple care settings.