This review, not intended as comprehensive, aims at: 1) providing brief key insights into proposed mechanisms of idiosyncratic DILI, focusing on drug-related risk factors (physiochemical and pharmacokinetic properties); b) using cyclin-dependent kinase (CDK)4/6 inhibitors, relatively novel oral anticancer medications approved for breast cancer, as a case study to discuss the feasibility of early detection of DILI signals during drug development. The gene discussed is CDK4; the disease is breast carcinoma.