The macrolides exhibit broad distribution in tissues and, in the case of some of the newer drugs, prolonged half-lives. The macrolides are also known for their intracellular accumulation within phagocytes. This chapter explains different types of macrolides approved for veterinary use: erythromycin, tylosin, spiramycin, tilmicosin, tulathromycin, gamithromycin, tildipirosin, and tylvalosin. Newer erythromycin derivatives with enhanced pharmacokinetic and in some cases broader antibacterial activities include roxithromycin, dirithromycin, clarithromycin, and azithromycin. The two most widely studied ketolides are telithromycin and cethromycin. The pharmacokinetics properties of ketolides include a long half-life as well as extensive tissue distribution and uptake into respiratory tissues and fluids, allowing for once-daily dosing. The chapter also explains antimicrobial activity, pharmacokinetic properties, toxicity and adverse effects, administration and dosage and clinical applications of macrolides, azalides, and ketolides.