Nature holds innumerable and often unexplored sources of chemical structures that have great potential for pharmacological applications. This project investigated plant-derived compounds for their potential use as new tuberculosis (TB) drugs. The challenges of TB drug development are attributed to the complexity of the disease: Mycobacterium tuberculosis (Mtb), the causal agent of TB, can reside in human tissues for decades without replicating, but with the potential of resuming growth and developing into active TB. Currently, there are no antibiotics that specifically target non-replicating Mtb. This project uses ethno-botanical knowledge to navigate the chemical diversity found in South African medicinal plants and to identify plant derived compounds with inhibitory activity against Mtb. While no plant extracts have previously been tested against non-replicating Mtb, our data demonstrates that compounds isolated from Warburgia salutaris (Canellaceae) are effective in killing both replicating and nonreplicating Mtb. Furthermore, the compound class drimane sesquiterpenes, characteristic of the Canellaceae family, was confirmed as being responsible for the demonstrated biological activity. Microarray studies were also completed to gain insight into the mechanism of action of drimane sesquiterpenes compounds in Mycobacteria. The data suggests that drimane compounds increase the expression of those genes involved in the general stress response of the bacteria. Additionally, some of the microarray data suggests that these compounds may be targeting the cell wall. !