A cumulative risk framework was used to examine the impact of the presence of multiple risk factors on key asthma outcomes (i.e., health-related quality of life [HRQoL], severity) for a sample of 149 inner-city African-American youth with asthma. The presence of a greater number of risk factors was associated with lower HRQoL and greater severity, regardless of age or gender. Cumulative risk methodology, in combination with selection of risk factors based on theoretical and empirical work, is a viable option for researchers and clinicians who are interested in examining the impact of multiple risk factors on disease functioning and status.