Strong antiviral and antimicrobial activities were detected in methanolic extracts of 24 plants used medicinally in the treatment of skin infections in four different regions of Colombia. Thirteen extracts displayed activity against herpes simplex virus (HSV) whereas none was active against poliovirus. The antiviral activity was indicated by a total inhibition of viral cytopathic effects (CPE) at a non-cytotoxic concentration of the extract. The most potent extract was obtained from Byrsonima verbascifolia (L.) HBK. which showed anti-HSV activity at a concentration as low as 2.5 microg/ml. Antimicrobial screening was conducted using the disc diffusion assay against Klebsiella pneumoniae, Escherichia coli, Streptococcus faecalis, Mycobacterium phlei, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and the human pathogenic yeast, Candida albicans. Anti-Candida activity was observed for Piper lanceaefolium HBK. and Juglans neotropica Diels. Twenty-two extracts displayed activity against Gram-positive bacteria whereas none was active against the Gram-negative species. We concluded that these Colombian medicinal plants represent an untapped source of potentially useful antivirals and are worthy of further study.