Experimental design and sample manipulation in the deep sea are extremely difcult, time consuming, and expensive. This is due to several factors, including the ship time and high technology required for carrying on experiments under high pressures and in the open ocean. So far, a very limited number of experiments has been conducted at depths >1000 m, and most of them have been carried out only in the last 30 years following the interest in the hydrothermal vents and cold seeps ecosystems. Some experiments have also been conducted on common soft deep-sea sediments and other habitats, but the experimental replication and overall quality of the information gathered from these studies is very low when compared with experiments carried out in shallow soft-bottom habitats or in the intertidal communities. Given the relevance of deep-sea ecosystems to global biogeochemical cycles, their key role in the overall functioning of the biosphere, and their fundamental contribution to the total global biodiversity, experimental manipulations are clearly needed in the future. It can also be anticipated that future investigations in the deep sea will follow the trend of development pointed out in other research elds, with a progressive increase of the importance of manipulative and experimental research when compared with descriptive studies and with an increase in the level of replication of the experiments, scale of investigation, and complexity of the phenomena investigated.