Active efflux of antibiotics mediated by multidrug transporters is a mechanistic basis of multidrug resistance in bacteria. The most versatile multidrug transporters are those found in Gram-negative bacteria. They have a high level of constitutive expression and provide an immediate response to structurally diverse antimicrobial agents including clinically important antibiotics. The versatility and efficiency of multidrug transporters in Gram-negative bacteria heavily depend on coupling of drug efflux with the transport across the outer membrane. The coupling is achieved through the assembly of multi-component protein complexes that span both the inner and the outer membranes of Gram-negative bacteria. In this review we discuss the mechanistic and structural features of multidrug efflux complexes with the major focus on the tight coupling of drug efflux with transport across the outer membrane.