A huge number of microorganisms are still unknown and remain uncultivated. Small subunit (SSU)rRNA/DNA-based analyses of complex microbial communities have revealed the diversity, distribution and abundance of uncultured microorganisms in natural environments. How to isolate these uncultivated microorganisms is an everlasting issue for microbiologists even when culture-independent functional analyses such as community genomics are becoming the prevailing trend. Although conventional isolation procedures are very laborious, there is still room for major improvements of the culture strategies. Symbiotic association between organisms provides important clues to systematically explore the uncultured microorganisms.