In oncology, a 2D in vitro model of cancer cell lines is still widely used for large-scale drug screening. However, most promising candidates firstly identified by in vitro analysis tend to fail during the next steps of drug development. The generation of an ex vivo approach termed ‘organoid’ is emerging as a promising preclinical model to mimic human tumors more accurately. In this review, we focus on human-derived organoid use for anticancer drug screening. We describe the development of this new in vitro model, its use for anticancer agent assays and the advantages compared with the currently used 2D models. Finally, we discuss organoid limitations in the common use of this technology during preclinical studies.