The aging demographic landscape of the United States highlights a concomitant rise in chronic conditions and infectious diseases. Older adults face a heightened susceptibility to infections, particularly pneumonia and urinary tract infections, and comorbidities such as cancer, cardiovascular disease, and dementia. Frailty, defined by a set of phenotypic criteria, emerges as a crucial predictor of adverse outcomes in infections, affecting hospitalization and post-care interventions. In the context of cancer, various frailty indices demonstrate their utility in predicting complications, mortality, and long-term outcomes. Cardiovascular diseases, including acute coronary syndrome and myocardial infarctions, exhibit varied associations with frailty, influencing both short-term and long-term prognosis. Frailty's impact extends to valvular heart disease, necessitating risk assessment and tailored care. In dementia patients, frailty is linked to cognitive decline, mortality, depression, and reduced daily living activities, emphasizing the need for holistic assessment and intervention. This review explores the role of frailty indices in predicting outcomes across diverse health conditions, with a focus on infections, cancer, cardiovascular disease, and dementia. Future interventions should address the role of frailty in predicting poor prognostic outcomes, including mortality, readmission rates, and complications across diverse health conditions.