One of the greatest challenges in biotechnology is the provision of novel chemical scaffolds for medicine and industry. The past two decades have witnessed major advances in our understanding of natural product biosynthesis, including the genetic basis for specialised metabolite production by a number of groups of bacteria, algae and fungi. Cyanobacteria (blue-green algae) produce an unparalleled array of bioactive small molecules, including some of which are potent toxins and potential therapeutics. Most cyanobacteria have drugs encoded within their genomes. Early work on the genetics of cyanobacteria has provided evidence of genetic recombination and possible gene transfer in aquatic environments. Genomic information has also indicated the cellular regulators of toxin production, as well as associated transport mechanisms. Exploiting what we refer to as toxins, such as saxitoxin and microcystin, are examples of the unlimited potential in natural product biosynthetic engineering for the creation of unnatural compounds useful as antibiotics, antivirals, and immunosuppressants. Current directions in bioprospecting from extremophilic microbes, along with the synthetic biology platform for small molecule design and sustainable production will be discussed as outcomes of our work to discover and produce novel and valuable chemicals, including sunscreens and food preservatives.