Tetracyclines have four cyclic rings in the structure. They are obtained from soil actinomycetes—Streptomyces aureofaciens. They inhibit gram positive (+ve), rickettsiae, chlamydiae, Mycoplasma and some protozoa. Hence are called broad spectrum antimicrobial agents (AMAs). Chloramphenicol is a broad spectrum antibiotic obtained from Streptomyces venezuelae. Mechanism of action, spectrum of activity, mechanism of resistance, pharmacokinetics, adverse effects, and drug interactions of both tetracyclines and chloramphenicol are discussed in this chapter.