This paper examines the associations between chronic disease, age, and physical and mental health-related quality of life (HRQOL), using data collected in 10 studies representing five chronic conditions. HRQOL was measured using the SF-36 or the shorter subset, SF-12. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were graphed by condition in age increments of 10 years, and compared to age- and sex-adjusted normative data. Linear regression models for the PCS and MCS were controlled for available confounders. The sample size of 2418 participants included 129 with renal failure, 366 with osteoarthritis (OA), 487 with heart failure, 1160 with chronic wound (leg ulcer) and 276 with multiple sclerosis (MS). For the PCS, there were large differences between the normative data and the mean scores of those with chronic diseases, but small differences for the MCS. Female gender and comorbid conditions were associated with poorer HRQOL; increased age was associated with poorer PCS and better MCS. This study provided additional evidence that, while physical function could be severely and negatively affected by both chronic disease and advanced age, mental health remained relatively high and stable.