To describe and understand the challenges of patients with chronic critical illness (CCI), their families and healthcare providers during the disease trajectory.; This qualitative study follows Thorne's methodology of interpretive description and was guided by the ethnographic method of observation and participation. Five cases, each comprising one patient with chronic critical illness their family members and several healthcare providers, were followed from the intensive care unit of a university hospital in Switzerland across different settings. In total, five patients with chronic critical illness, 12 family members and 92 healthcare providers (nurses, nursing students, care assistants, physiotherapists and occupational therapists and physicians) were observed.; Regardless of the medical diagnoses and disease trajectories of the patients with chronic critical illness, all cases faced three main challenges: 1. Dealing with the unpredictability of the disease trajectory beyond the underlying disease. 2. Coping with the complexity of care. 3. Perceiving communication challenges despite all involved parties' dependency on it.; Unpredictability is not only a unique characteristic of the prolonged disease trajectory of patients with chronic critical illness, but also one of the main challenges of the participants. Therefore, the way unpredictability is handled is dependent on changes in the complexity of care and communication, highlighting the need for participation, information, empathy, clarity and honesty among all participants.