H3ABioNet is composed of 28 different Nodes based in 17 countries, 16 in Africa and 1 in the USA. It is led by the Principal Investigator, Prof Nicola Mulder, at the University of Cape Town. Each Node has a Node Principal Investigator (PI) that is part of the General Assembly (GA).

H3ABioNet activities are organized into 8 workpackages:

Each Workpackage is headed by a Chair and a Co-Chair, which belong to the Management Committee (MC). The MC meets monthly to report on projects within the workpackages. The MC sets priorities, monitors deliverables and timelines, allocates resources, and reviews applications for courses or internships. The MC communicates decisions to the GA at quarterly meetings.

The GA is responsible for high-level strategic planning for the network, maximising the synergies between the project components, reviewing node status and progress and fund-raising. The GA meets quarterly with an annual face-to-face network meeting. Each member of the GA has equal voting rights, with 1 vote per Node.

The GA reports to the Scientific Advisory Board (SAB), which provides input and advice on overall strategic goals and management. The GA, with input from the SAB, monitors progress of each Node and ensures that each group is carrying its own weight within the network.