Myxobacteria produce a range of structurally novel natural products which exhibit unusual or unique modes of action, attracting significant interest from both the academic and drug discovery communities. Efforts to discover new strains with the potential to biosynthesize novel molecules have revealed that myxobacterial diversity and natural products are far from exhausted. We describe here a general, nonselective approach to unearth further myxobacterial strains, in order to mine them for compounds with potential as medicines. Sample collection from locations world-wide has shown that environments which exhibit significant biological complexity yield the highest probability of isolating novel myxobacterial strains. Here, we illustrate the details of simple and efficient strain purification techniques, which lead systematically to the identification of new and promising myxobacteria. Compound identification is then facilitated by molecular biological approaches, coupled with sophisticated high resolution mass spectrometry, statistical analysis, and bioassays.