A clear understanding of the processes by which pathogens interact with their hosts at the cellular and molecular level can be used to inform the design and development of potential therapeutic interventions. Pivotal to this endeavour in developing treatments for malaria is revealing mechanisms by which merozoites recognise, attach to and invade the host erythrocyte, and how host cells play more than a bystander role in this process. We have identified an essential ligand –Rh5 – that governs erythrocyte entry. Furthermore, we have shown that Rh5 acts in complex with two other critical factors to drive invasion. In this presentation, I will demonstrate how this protein complex functions to allow P. falciparum to gain access to the inside of the red blood cell and furthermore, show how antibodies that target the Rh5 complex block key interactions to prevent invasion. Our work highlights how a combination of molecular genetics, structural biology and antibody studies not only reveals fascinating biology of this insidious pathogen but also provides a critical insight into developing next-generation vaccines to combat this devastating disease.