The available literature on the secondary or nonessential metabolites of the streptomycetes bacteria suggests that there may be poorly expressed or "cryptic" compounds that have yet to be identified and that may have significant medical utility. In addition, it is clear that there is a large and complex regulatory network that controls the production of these molecules in the laboratory and in nature. Two approaches that have been taken to manipulating the yields of secondary metabolites are the use of various stress responses and, more recently, the use of precision chemical probes. Here, we review the status of this work and outline the challenges and opportunities afforded by each of them.