In recent years, with the widespread application of high-throughput screening technologies in drug discovery, an increasing number of new chemical entities with extremely poor aqueous solubility have been generated. Their poor solubility represents a major challenge for formulation of these compounds for both oral and parenteral administration. Formulations for intravenous (i.v.) application are of significant importance because they are frequently used in several key therapeutic areas, such as oncology and anesthesia. Furthermore, i.v. formulations of new compounds are often needed to determine basic biopharmaceutical parameters and to obtain proof of concept results in the early phase of product development. This review provides an overview of the recent advances in formulation approaches and drug delivery technologies for poorly water-soluble compounds applicable to i.v. administration. The advantages and disadvantages of different strategies are highlighted and an expert opinion on each technical field is presented.