© Springer International Publishing Switzerland 2016. The application of metagenomics technologies to the area of marine bioprospecting and biodiscovery has seen a major advance in our capacity to harness the bioactive potential of the ocean, not least when we consider the limitations surrounding culturability of microorganisms from this and other ecosystems. Combining genomics, bioinformatics, and systems biology, metagenomics has provided new levels of access to the rich tapestry of novel bioactivities from the marine microbiome. Notwithstanding this early promise, considerable limitations to the technology exist that currently prevent us from harnessing the full potential of marine microbial natural products. The continued growth in the number and diversity of metagenomic studies, allied with the advances in next generation sequencing platforms, has brought with it a global appreciation of the challenges that need to be addressed to ensure future developments in this applied research area. In this chapter we present the application of metagenomics for biodiscovery, discussing the potential value of this technology, and the current limitations preventing its full realization. Already, advances in bioinformatics, robotics, molecular cloning and expression, DNA sequencing and isolation, as well as the continued development of improved chemical profiling systems, have led to the discovery of new natural products and bioactivities. Successful implementation of further improvements that circumvent current bottlenecks will open new horizons for medical and industrial developments.