A situational analysis of problematic situations was conducted for 37 caregivers of children with sickle cell disease (SCD) who ranged in age from 5 to 13 years. Participants responded to a semistructured interview related to caring for a child with SCD. The interview included the domains of medication adherence, nutrition, minimizing and coping with pain episodes, social problems, academic difficulties, and children's expression of negative feelings related to having SCD. Caregivers described a total of 356 problems. Almost all caregivers reported experiencing problems with their children's nutrition (n = 35), minimizing pain episodes (n = 34), and their children expressing feelings about having SCD (n = 33). Moderately challenging and emotionally upsetting problems were reported for coping with pain episodes. The total number of problems was significantly higher for boys than for girls. Nutrition issues were more frequently reported for younger children. Findings have salient clinical implications for the care of children with SCD.