Organoids are multicellular structures that can be derived from adult organs or pluripotent stem cells. Early versions of organoids range from simple epithelial structures to complex, disorganized tissues with large cellular diversity. The current challenge is to engineer cellular complexity into organoids in a controlled manner that results in organized assembly and acquisition of tissue function. These efforts have relied on studies of organ assembly during embryonic development and have resulted in development of organoids with multilayer tissue complexity and higher order functions. Coupled with patient-derived stem cells, my group studied the mechanisms of human hepatic diseases that includes viral hepatitis, steatohepatitis, recently extended to drug induced liver injury (DILI), wherein organoid modelled the clinical phenotype and genotype are correlated. Here I will summarize the next generation of organoid by design, and discuss its promise and impact to elucidate personalized disease mechanisms and understand drug reactions underlying individual variations in humans.