In this second article of our two-part review, we focus on age-associated physiologic changes involving the nervous, endocrine, hematologic, immune, and musculoskeletal systems, with close attention to the interconnected nature of these systems. There is a well-known connection between the neuroendocrine and immune systems via the hypothalamic-pituitary-adrenal axis and via interaction by means of cytokines, hormones, and neurotransmitters. These changes may lead to a loss of integration and resiliency with age, thus decreasing the ability of the elderly patient with cancer to adapt to stressful circumstances. Prominent changes include decline in memory and cognition, and increased susceptibility to peripheral neuropathy. Hematologic and immune changes like reduced bone marrow reserve and increased susceptibility to infections have far reaching implications for cancer care in the elderly. Gradual decline in hormone levels, and changes in muscle and body composition, can lead to functional decline and frailty. Use of the clinical interventions suggested in this article, along with an appreciation of the interplay of these age-related physiologic changes and their consequences, allows oncology professionals to customize therapy and minimize side effects in the geriatric oncology patient.