Designing artificial microtissues by reaggregation of monodispersed primary cells, neoplastic or engineered cell lines is providing insight into cell-cell interactions and underlying regulatory networks. Recent advances in microtissue production have highlighted the potential of scaffold-free cell aggregates in maintaining tissue-specific functionality, supporting seamless integration of implants into host tissues, and providing complex feeder structures for difficult-to-differentiate cell types. Furthermore, these tissues are amenable to therapeutic and phenotype-modulating interventions using latest-generation transduction technologies. Microtissues produce therapeutic transgenes at increased levels and offer tissue-like assay environments to improve drug-function correlations in current discovery programs. Here, we outline scaffold-free microtissue design in liver, heart and cartilage, and discuss how this technology could significantly impact regenerative medicine.