INTRODUCTION: Mentoring programs are frequently recommended as innovative and low-cost solutions, and these have been implemented in many healthcare institutions to tackle multiple human resource-related challenges. This review sought to locate, appraise and describe the literature reporting on mentorship programs that were designed to improve healthcare worker competence and institutional performance in Africa. METHODS: This review searched and synthesized reports from studies that assessed the effectiveness of mentorship programs among healthcare workers in Africa. We searched for studies reported in the English language in EMBASE, CINAHL, COCHRANE and MEDLINE. Additional search was conducted in Google Scholar. RESULTS: We included 30 papers reporting on 24 studies. Diverse approaches of mentorship were reported: a) placing a mentor in health facility for a period of time (embedded mentor), b) visits by a mobile mentor, c) a mentoring approach involving a team of mobile multidisciplinary mentors, d) facility twinning, and e) within-facility mentorship by a focal person or a manager. IMPLICATION FOR PRACTICE: Mentoring interventions were effective in improving the clinical management of infectious diseases, maternal, neonatal and childhood illnesses. Mentoring interventions were also found to improve managerial performance (accounting, human resources, monitoring and evaluation, and transportation management) of health institutions. Additionally, mentoring had improved laboratory accreditation scores. Mentoring interventions may be used to increase adherence of health professionals to guidelines, standards, and protocols. While different types of interventions (embedded mentoring, visits by mobile mentors, facility twinning and within-facility mentorship by a focal person) were reported to be effective, there is no evidence to recommend one model of mentoring over other types of mentoring. IMPLICATIONS FOR RESEARCH: Further research-experimental methods measuring the impact of different mentoring formats and longitudinal studies establishing their long-term effectiveness-is required to compare the effectiveness and cost-effectiveness of different models of mentoring. Further studies are needed to explore why and how different mentoring programs succeed and the meaningfulness of mentoring programs for the different stakeholders are also required.