ATP binding cassette (ABC) transporters are a ubiquitous superfamily of integral membrane proteins that mediate the translocation of various substrates across membranes using ATP hydrolysis. The highly conserved ABC domains drive the transport process, while the transmembrane domains form the translocation pathway. Recent structural advances in prokaryotic ABC transporters have provided a molecular framework for understanding the transport cycle. The goal is to develop quantitative models that detail the kinetic and molecular mechanisms by which ABC transporters couple ATP binding and hydrolysis to substrate translocation. ABC transporters are essential for cellular survival, as they facilitate the import of essential nutrients and the export of waste products. They are present in all kingdoms of life, with the largest families found in *Escherichia coli* and humans. The structural architecture of ABC transporters consists of four domains: two transmembrane domains (TMDs) and two ABC domains (NBDs). The TMDs interact with the helical domains of the ABC domains through coupling helices, and their conformational changes drive substrate translocation. The ABC domains pack together in a "head-to-tail" fashion, with the binding site for nucleotides positioned at the subunit-subunit interface. The ATPase activity of ABC transporters is regulated by the binding of allosteric ligands, and the active site residues are organized in a bipartite manner, allowing control of nucleotide hydrolysis. Understanding the detailed mechanisms of ABC transporters will enhance our ability to develop therapeutic agents and appreciate the fundamental processes that govern molecular movement across membranes.ATP binding cassette (ABC) transporters are a ubiquitous superfamily of integral membrane proteins that mediate the translocation of various substrates across membranes using ATP hydrolysis. The highly conserved ABC domains drive the transport process, while the transmembrane domains form the translocation pathway. Recent structural advances in prokaryotic ABC transporters have provided a molecular framework for understanding the transport cycle. The goal is to develop quantitative models that detail the kinetic and molecular mechanisms by which ABC transporters couple ATP binding and hydrolysis to substrate translocation. ABC transporters are essential for cellular survival, as they facilitate the import of essential nutrients and the export of waste products. They are present in all kingdoms of life, with the largest families found in *Escherichia coli* and humans. The structural architecture of ABC transporters consists of four domains: two transmembrane domains (TMDs) and two ABC domains (NBDs). The TMDs interact with the helical domains of the ABC domains through coupling helices, and their conformational changes drive substrate translocation. The ABC domains pack together in a "head-to-tail" fashion, with the binding site for nucleotides positioned at the subunit-subunit interface. The ATPase activity of ABC transporters is regulated by the binding of allosteric ligands, and the active site residues are organized in a bipartite manner, allowing control of nucleotide hydrolysis. Understanding the detailed mechanisms of ABC transporters will enhance our ability to develop therapeutic agents and appreciate the fundamental processes that govern molecular movement across membranes.