This study evaluated the extent to which schizophrenia and its treatment interferes with participation in valued life activities and its impact on subjective well-being. The Illness Intrusiveness Ratings Scale was completed by 78 individuals with schizophrenia on 3 measurement occasions. Clinicians working with participants, plus a relative/friend of each participant also provided independent ratings of the person. The Illness Intrusiveness Ratings Scale displayed internal consistency (coefficient α = 0.82), and temporal stability across 1 day (r = 0.89), 1 week (r = 0.51), and 1 month (r = 0.78). Reported intrusiveness was high (M = 50.5) and was among the highest compared with populations with other serious medical and psychiatric illnesses. Ratings correlated with staff and family/friends’ ratings of intrusiveness (r = 0.33 and r = 0.40), measures of symptomatology (average r = 0.25), and subjective well-being (average r = 0.41). Path analysis indicated that lifestyle disruption mediates the impact of symptoms and treatment on well-being. Implications for these findings and future directions for research are discussed.