The design of a new chemotherapeutic agent, suitable for clinical use in the treatment of human infections, must take into account two aspects above all others. First, the drug must possess high antimicrobial activity and secondly it must be non-toxic to human tissue. Paul Erlich’s early concept of a selectively toxic ‘magic bullet’ is thus just as true in the modern world as when it was first propounded. A host of antimicrobial agents has been examined and many shown to be effective inhibitors of micro-organisms in vitro; unfortunately, several of these have been found to be harmful to human tissues and consequently have no role to play in chemotherapy. This chapter will thus concentrate on several of those chemotherapeutic agents that have proved their worth when employed internally (usually orally or parenterally). Antimicrobial compounds that are used for their disinfectant, antiseptic or preservative qualities will not be dealt with here.