Microorganisms have mechanisms that enable them to tolerate lethal concentrations of toxic compounds. This feature has been exploited in a wide range of bioprocesses that range from bioremediation applications to production of fine chemicals in two-phase reaction media. The ability to modify the physical properties of cellular membranes has long been put forward as a protection mechanism that enables microorganisms to tolerate solvents. More recently, efflux pumps have been shown to extrude deleterious compounds, such as antibiotics, drugs and solvents. An understanding of the mechanism of solvent tolerance and its relationship to cross-resistance of pathogenic organisms to antibiotics has major impact on the type and use of disinfectants and disinfecting procedures. The presence of solvents in the growth environment may lead to the emergence of solvent resistant strains and, therefore, overuse may propagate resistant microbial variants. In this paper, mechanisms that lead to solvent tolerance of microbes and accompanying specific antibiotic resistance are reviewed.