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A highly-effective, long-lasting vaccine, targeting multiple stages of the Plasmodium falciparum life cycle, is likely to be important for the elimination of this pathogen. Key antigens of this vaccine would produce host antibodies that block the ligands required for merozoite invasion of erythrocytes, thereby curtailing the expansion of parasitemia and symptomatic disease. Recent live cell imaging of invading Plasmodium falciparum merozoites with various receptor-ligand interactions inhibited has provided new information about the function, sequence, and timing of these events, providing a rationale for a vaccine containing multiple antigens that inhibit the sequential steps of invasion.