The genus Eriocephalus, commonly known as ‘wild rosemary', ‘Cape snow bush', ‘kapokbos' or ‘asmabossie', belongs to the family Asteraceae, of the tribe Anthemideae. It is endemic to southern Africa and is comprised of 32 species, of which several are economically important as traditional herbal remedies and as perfumes in fragrance industries. The species may be an important potential source for new and novel drugs for the treatment of various diseases, hence warrants further research. An investigation into the antimicrobial activity of the genus Eriocephalus using the disc diffusion assay against a range of Gram-positive and Gram-negative bacteria as well as a few selected fungi was carried out. The study included 15 Eriocephalus species with 113 essential oil and acetone leaf extract samples. Preliminary screening was carried out using 16 test pathogens: Bacillus cereus, B. subtilis, Staphylococcus aureus (four strains), S. epidermidis, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Salmonella typhimurium, S. enteriditis, Proteus vulgaris, Serratia odorifera, Enterococcus faecalis, Cryptococcus neoformans, Candida albicans and Alternaria alternata. From the preliminary screening, the most susceptible test pathogens selected for further study were: Bacillus cereus, B. subtilis, Staphylococcus aureus (one strain), Klebsiella pneumoniae, Escherichia coli, Cryptococcus neoformans and Candida albicans. The Gram-positive bacteria and two fungal pathogens showed inhibition for most of the essential oils and the leaf extracts while there was very little activity noted on the Gram-negative bacteria. Intra- and inter-population variation as well as inter-specific variation was observed in the antimicrobial activity for some species of Eriocephalus. The major variation was mainly observed in the activity of the essential oils and the leaf extracts against the yeast, Cryptococcus neoformans and the Gram-positive bacteria, Bacillus cereus, B. subtilis and Staphylococcus aureus. From the results obtained from the disc diffusion assay, the most active species were selected to determine the minimum inhibitory concentration against two Gram-positive and two Gram-negative bacteria and two fungal strains. The acetone extracts of E. aromaticus from Swartberg produced the most promising activity for all species studied with MIC values of 400μg ml-1 and 200μg ml-1 for B. cereus and S. aureus respectively.