Publisher Summary This chapter presents an overview of the research work conducted to analyze the invasion of erythrocytes in case of malaria. In 1969, the invasion of erythrocytes by merozoites was described in electron microscopic studies. With improvements in electron microscopy techniques and membrane sieving methods that allowed for isolation of large numbers of Plasmodium knowlesi merozoites, a detailed description of the morphological characteristics of invasion was achieved. As other electron microscopic studies have shown similar structural characteristics for erythrocytic merozoites, it is assumed that the steps in invasion are similar for all the species of malaria parasites including Plasmodium falciparum and Plasmodium vivax. In an elegant series of studies using both videomicroscopy and electron microscopy, the dynamics of the entry process have been described in considerable detail. The earliest light microscopic investigations, as well as the visualization of the steps in invasion that suggest the presence of parasite ligands and red cell receptors are discussed. The experimental study using in vitro short-term culture system to study invasion is described. An overview of the human Duffy antigen is also presented.