Over thirty years of studies have established that conjugative transfer of plasmid-encoded resistance to drugs and heavy metals can take place at high frequency between various organisms under laboratory conditions. The detected transfer frequencies in soil, in aquatic environments, and in the urogenital and respiratory tracts of healthy animals and man have generally been low. However, the conversion of bacteria from susceptible to resistant to antibiotics has been observed often during antimicrobial therapy. This has formed a challenge for the antibacterial treatment of pathogenic bacteria and called for the evaluation of the extent of conjugative transfer in various environments. Several biochemical and physicochemical factors inhibit conjugation, show preferential toxicity against plasmid-bearing cells, or stimulate plasmid curing. These factors include various agents such as detergents, anesthetics, mutagens and antibiotics which affect membrane potential, membrane permeability, protein synthesis and the processing of DNA. The application of the data on these agents, summarized in this review, might be helpful in preventing drug multi-resistance from spreading. Also these data might be valuable in studies which use conjugation as a tool or which treat the molecular mechanisms involved in conjugation.