Drug discovery and development has always been a complex business even when medicines were almost exclusively small organic molecules. At the time of writing, a quarter of a century has elapsed since the beginning of the new millennium. The once novel therapeutics, such as monoclonal antibodies, emerged in the last decade or so of the twentieth century and are now firmly established in the top sales ranks of branded prescription medicines worldwide. More recently, gene therapies and nucleic acid-based drugs have reached the clinic along with cell therapies that were once considered unthinkable as pharmaceutical products. There is great promise in these new approaches, but also great challenges to be overcome, particularly when trying to expand the use of these quite exotic technologies to treat the many millions of patients who suffer from common diseases. The following chapters review the current status of emerging approaches to drug discovery and development. Some of these will ultimately prove to be unviable, while hopefully many others will be successful and reduce the burden of disease and even be curative.