The newer macrolide antibiotics overcome some of the major drawbacks of erythromycin, such as acid instability and poor pharmacokinetic behavior. Nonetheless, they retain the classic clinical applications of the older compounds, including activity against intracellular pathogens (eg, Legionella, Chlamydia, and Rickettsia species). Their good pharmacokinetic properties and tissue distribution mean that macrolides may prove useful in more unusual settings such as infections due to mycobacteria and protozoa (eg, Toxoplasma gondii, Entamoeba histolytica, Pneumocystis carinii, and Plasmodium falciparum). Other potential target infections are chronic gastritis (Helicobacter pylori) and borreliosis (Borrelia burgdorferi). It may, however, prove necessary to combine the macrolide with another anti-infective for reasons of efficacy or to prevent selection of resistant mutants. A major step forward would be the development of compounds that are not cross-resistant with erythromycin.