Mining of natural sources for new secondary metabolites has a successful history, which is reflected by the fact that over 50% of all drugs, currently on the market, are derived from natural products. Bacteria are one of the most important sources of bioactive natural products destined for drug discovery. However, less than 1% of the microorganisms observed in different habitats have been cultivated and characterized. To explore the genomic and functional diversity of the vast majority of the microbial world, novel methods were introduced, which are based on analysis of a DNA isolated from environmental communities. Metagenomics represents a strategy offering access to the genetic information present in uncultured bacteria by screening of libraries constructed from DNA isolated from different habitats. Functional-and sequence-driven screens are the major approaches employed to mine metagenomic libraries. This review aims to highlight discoveries in this area and discusses the possible future directions of the field.