Background and Objectives: Children with asthma who have depressed caregivers are known to be less adherent to medication regimes. However, it is less clear how adherence responds to a caregiver’s new diagnosis of severe depression or whether there is a similar relationship with other serious caregiver diagnoses. The hypothesis is that adherence worsens both with new diagnoses of depression and possibly with new diagnoses of other serious conditions. Methods: This study follows a cohort of 341,444 continuously insured children with asthma before and after a caregiver’s new diagnosis of severe depression or another serious health condition. The effect of a new depression diagnosis on a child’s medication adherence is compared to the effect of new diagnoses of other common caregiver chronic conditions including diabetes, cancer, congestive heart failure, coronary artery disease, and chronic obstructive pulmonary disease. Results: Results show that children’s medication adherence declines following a caregiver’s new diagnosis of severe depression, but that it also declines following a caregiver’s new diagnosis of diabetes. There is no association with new diagnoses of the other caregiver chronic conditions examined. Conclusions: Children whose caregivers have a new diagnosis of depression or diabetes may be at increased risk of deterioration in their medication adherence. These caregivers may benefit from additional support and follow-up. The relationship between caregivers’ health and children’s medication adherence is complex and deserves further study.