Streptomyces are Gram-positive, soil-dwelling bacteria that are prolific producers of antibiotics. Most of the antibiotics used in clinical and veterinary medicine worldwide are produced as natural products by members of the genus Streptomyces. The regulation of antibiotic production in Streptomyces is complex and there is a hierarchy of regulatory systems that extends from the level of individual biosynthetic pathways to global regulators that, at least in some streptomycetes, control the production of all the antibiotics produced by that organism. Ribonuclease III, a double-strand specific endoribonuclease, appears to be a global regulator of antibiotic production in Streptomyces coelicolor, the model organism for the study of streptomycete biology. In this review, the enzymology of RNA degradation in Streptomyces is reviewed in comparison with what is known about the degradation pathways in Escherichia coli and other bacteria. The evidence supporting a role for RNase III as a global regulator of antibiotic production in S. coelicolor is reviewed and possible mechanisms by which this regulation is accomplished are considered.