Background: As in other countries, Danish health authorities have introduced disease management programmes (DMPs) to improve care quality. These contain clinical practice guidelines (CPGs) and guidelines for patient stratification based on doctors' assessments of disease severity and self-care. However, these programmes are challenged when patients have complex chronic conditions. Aim: To explore how GPs experience the clinical applicability of disease management programmes for patients with multiple chronic conditions and lowered self-care ability. Design & setting: A qualitative study from general practice, conducted in rural areas of Denmark with economically disadvantaged populations. Method: Data were collected through case-based, semi-structured interviews with 12 GPs. The principles of systematic text condensation were used in the analysis. Results: GPs found DMPs inadequate, particularly for patients with multiple conditions and lowered self-care ability. Their experience was that adhering to multiple programmes' CPGs resulted in too much medication, conflicting treatments, an overload of appointments, and fragmented health care. They disregarded stratifying according to guidelines because they deemed stratification criteria to reflect neither patients' need for self-care support, nor flexible referral options to hospitals and municipalities. Therefore, GPs were often solely responsible for treatment of patients with very complex chronic conditions. Conclusion: GPs found DMPs to be of limited clinical applicability due to challenges related to CPGs, patient stratification, and lack of adequate health services to support patients with complex healthcare needs. To increase the benefits of these programmes, they should be more flexible, and adjusted to the needs of patients with multiple chronic conditions and lowered self-care ability.