Rab GTPases are key regulators of intracellular membrane traffic and cell physiology. They control all steps of membrane transport, from vesicle formation to fusion, by interacting with effector proteins that select cargo, promote vesicle movement, and ensure correct fusion. Rab dysfunction can lead to various diseases, including infectious diseases and cancer. Rab proteins cycle between the cytosol and their respective membranes, with their nucleotide-bound state influencing their localization and activity. Rab proteins are regulated by a network of proteins, including GDI, REP, GAPs, and GEFs, which facilitate their prenylation, activation, and inactivation. Structural studies have revealed how Rab proteins interact with their effectors and how their different domains contribute to their specific functions. Rab effectors are involved in various steps of membrane traffic, including cargo selection, vesicle movement, tethering, and fusion. Rab cascades ensure the transition between different Rab-defined compartments, with specific Rab proteins being activated or inactivated to generate a programmed transition. Rab proteins also play a role in membrane fusion by interacting with SNARE proteins or proteins that regulate SNARE function. Rab dysfunction can lead to disease, and intracellular pathogens can exploit the Rab regulatory system to evade host defenses. The study of Rab proteins and their interactions with effectors and other regulatory proteins is essential for understanding the complex network of membrane traffic and its role in cell physiology.Rab GTPases are key regulators of intracellular membrane traffic and cell physiology. They control all steps of membrane transport, from vesicle formation to fusion, by interacting with effector proteins that select cargo, promote vesicle movement, and ensure correct fusion. Rab dysfunction can lead to various diseases, including infectious diseases and cancer. Rab proteins cycle between the cytosol and their respective membranes, with their nucleotide-bound state influencing their localization and activity. Rab proteins are regulated by a network of proteins, including GDI, REP, GAPs, and GEFs, which facilitate their prenylation, activation, and inactivation. Structural studies have revealed how Rab proteins interact with their effectors and how their different domains contribute to their specific functions. Rab effectors are involved in various steps of membrane traffic, including cargo selection, vesicle movement, tethering, and fusion. Rab cascades ensure the transition between different Rab-defined compartments, with specific Rab proteins being activated or inactivated to generate a programmed transition. Rab proteins also play a role in membrane fusion by interacting with SNARE proteins or proteins that regulate SNARE function. Rab dysfunction can lead to disease, and intracellular pathogens can exploit the Rab regulatory system to evade host defenses. The study of Rab proteins and their interactions with effectors and other regulatory proteins is essential for understanding the complex network of membrane traffic and its role in cell physiology.