Initiatives to address the human resource crisis in African health systems have included expanded training of mid-level workers (MLWs). Currently, MLWs are the backbone of many health systems in Africa but they are often de-motivated and they often operate in circumstances in which providing high quality care is challenging. Therefore, assuming that introducing additional people will materially change health system performance is unrealistic. We briefly critique such unifocal interventions and review the literature to understand the factors that affect the motivation and performance of MLWs. Three themes emerge: the low status and inadequate recognition of MLWs, quality of care issues and working in poorly managed systems. In response we propose three interrelated interventions: a regional association of MLWs to enhance their status and recognition, a job enrichment and mentoring system to address quality and a district managers' association to improve health systems management. The professionalisation of MLWs and district managers to address confidence, self-esteem and value is considered. The paper describes the thinking behind these interventions, which are currently being tested in Kenya, Nigeria, South Africa and Uganda for their acceptability and appropriateness. We offer the policy community a complementary repertoire to existing human resource strategies in order to effect real change in African health systems.