Introduction: Laboratory mentoring programmes can be an important vehicle to establish and solidify quality management systems and help laboratories achieve accreditation goals. Different mentoring approaches have been used with varying levels of success. The authors provide a guide to implementing a structured laboratory mentorship programme based on their practical field experience. Method: The study is based on experience in Lesotho as well as subsequent roll out of a similar approach in the other African countries of Zimbabwe, Mozambique, Swaziland and Cameroon between 2009 and 2011. Summary: We highlight critical elements to consider when setting up a long-term, sustainable and well-structured mentorship programme. These elements include: well-defined goals; sufficient length of mentor engagement on site; standardised approach across laboratories; measurement of progress using standardised tools; well-structured reporting mechanisms; alignment of the programme with overall Ministry of Health plans; and selection and training of the mentors. These elements will differ in application, depending on countries’ needs and available resources. A structured approach allows for scalability, comparison across laboratories and countries and an easier approach to budgeting and planning for countries intending to set up similar programmes.