How do bacterial toxins associate with membrane rafts? Cell membranes are composed of over ten thousand types of lipids. Certain lipids are organized into clusters or domains, giving nanoscale regions of membranes different mechanical and geometric properties compared to the rest of the membrane. The most prominent form of organized membrane regions are lipid rafts, which are cholesterol-rich regions hypothesized to form by phase separation of lipids. Pathogens such as bacteria secrete toxins, which interact with lipid rafts to allow entry of the bacteria into host cell. Mechanisms by which such bacterial toxins associate with rafts are currently not well understood. We investigated the mechanism of raft association of two bacterial toxins, Cholera toxin B (CTxB) and vacuolating toxin A (VacA), secreted by Helicobacter pylori. Both CTxB and VacA are oligomeric proteins that associate with lipid rafts. CTxB is a pentamer, which binds five gangliosides and we found that recruitment of CTxB to rafts is dependent on its ability to crosslink gangliosides. Such crosslinking of gangliosides further stabilizes the membrane rafts themselves to further recruit CTxB. VacA has a more complex association with rafts. In contrast to CTxB, oligomerization of VacA is not essential for its raft association. In addition, distinct aspects of VacA association with the plasma membrane are likely mediated by binding to a protein receptor. Binding of VacA to lipid rafts is kinetically driven, while binding to non-raft phase is likely thermodynamically driven and occurs at longer timescales. The two toxins with different mechanisms of binding to rafts have provided insights into how bacterial pathogens exploit host machinery for cell entry and pathogenesis.