A theme of personalized medicine was highlighted at the 2009 Annual Meeting of the American Society of Clinical Oncology. To this end, the current review focuses on the impact of host characteristics (such as age, sex, and comorbidity) as they pertain to cancer biology, treatment efficacy, and tolerance. Increasing age is associated with complex changes in physiology, including alterations in renal and hepatic function, and decreased bone marrow reserve. These may in turn result in alterations in pharmacokinetics and toxicity related to many commonly used anticancer agents. Using tools, such as the geriatric assessment, may help to elucidate the physiologic age of the patient as opposed to the chronologic age. Increasing age is paralleled by an increase in comorbidity, and comorbidity may have independent prognostic implications and substantially impact medical decision making in the patient with cancer. Numerous biologic ties between cancer and comorbidity exist, one example being an association of diabetes with an increased risk of disease recurrence and mortality in the setting of colon cancer. Biologic features can also vary by sex; several biomarkers with either prognostic or predictive value (ie, excisionrepair cross-complementation group 1 expression, epidermal growth factor receptor mutation, or dihydropyrimidine dehydrogenase polymorphism) may differentiate efficacy or toxicity in males and females. Taken together, age, sex, and comorbidity each encompass a complex array of physiologic and molecular variations that may each aid in personalizing care for the patient with cancer.